scholarly journals Intracellular Delivery of Nanoparticles via Microelectrophoresis Technique: Feasibility demonstration

2020 ◽  
Author(s):  
Mengke Han ◽  
Jiangbo Zhao ◽  
Joseph Mahandas Fabian ◽  
Sanam Mustafa ◽  
Yinlan Ruan ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Membrane Damage ◽  
Hydrodynamic Diameter ◽  
Target Cells ◽  
General Strategy ◽  
Human Embryonic Kidney Cells ◽  
Cell Membrane Damage ◽  
Biological Studies

ABSTRACTNanoparticles with desirable properties and functions have been actively developed for various bio-medical research, such as in vivo and in vitro sensors, imaging agents and delivery vehicles of therapeutics. However, an effective method to deliver nanoparticles into the intracellular environment is a major challenge and critical to many biological studies. Current techniques, such as intracellular uptake, electroporation and microinjection, each have their own set of benefits and associated limitations (e.g., aggregation and endosomal degradation of nanoparticles, high cell mortality and low throughput). Here, the well-established microelectrophoresis technique is applied for the first time to deliver nanoparticles into target cells, which overcomes some of these delivery difficulties. Semiconductive quantum dots, with average hydrodynamic diameter of 24.4 nm, have been successfully ejected via small electrical currents (−0.2 nA) through fine-tipped glass micropipettes as an example, into living human embryonic kidney cells (roughly 20 - 30μm in length). As proposed by previous studies, micropipettes were fabricated to have an average tip inner diameter of 206 nm for ejection but less than 500 nm to minimize the cell membrane damage and cell distortion. In addition, delivered quantum dots were found to stay monodispersed within the cells for approximately one hour. We believe that microelectrophoresis technique may serve as a simple and general strategy for delivering a variety of nanoparticles intracellularly in various biological systems.

A reinvestigation of the function of the mammalian urinary bladder

1977 ◽  
Vol 232 (3) ◽  
pp. F187-F195 ◽  
Author(s):  
S. A. Lewis
Keyword(s):  
Urinary Bladder ◽  
Membrane Surface ◽  
Apical Cell ◽  
Membrane Damage ◽  
In Vitro Experiments ◽  
Apical Cell Membrane ◽  
Cell Membrane Damage ◽  
Using Data

The function of adult mammalian urinary bladder is evaluated in light of recent in vitro experiments. The discrepancy between in vivo and in vitro experimental results is examined and a possible solution proposed. Techniques for eliminating edge damage and measuring apical membrane surface area are described. A new chamber design for microelectrode studies is illustrated. The possibility of apical cell membrane damage caused by microelectrodes is critically examined and tested using the polyene antibiotic Nystatin. Using data from transepithelial and microelectrode experiments, a model for net Na+ transport across the bladder is proposed and then critically analyzed. The possible clinical implications of the in vitro experiments are briefly discussed.

scholarly journals Quercetin Rejuvenates Sensitization of Colistin-Resistant Escherichia coli and Klebsiella Pneumoniae Clinical Isolates to Colistin

2021 ◽  
Vol 9 ◽  
Author(s):  
Yishuai Lin ◽  
Ying Zhang ◽  
Shixing Liu ◽  
Dandan Ye ◽  
Liqiong Chen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Alternative Pathway ◽  
Membrane Damage ◽  
New Drugs ◽  
Colistin Resistance ◽  
Cell Membrane Damage ◽  
E Coli

Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant Escherichia coli (E. coli) and Klebsiella Pneumoniae (K. pneumoniae). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant E. coli and K. pneumoniae, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of mcr-1 and mgrB that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant E. coli and K. pneumoniae both in vitro and in vivo. Therefore, our results may provide an efficient alternative pathway against colistin-resistant E. coli and K. pneumoniae infections.

Abstract 130: Ox-LDL Impairs The Survival Of Bone Marrow Stem Cells Partially Through Membrane Damage Independent Of ROS Production In Vitro

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Xin Li ◽  
Yuan Xiao ◽  
Yuqi Cui ◽  
Hua Zhu ◽  
Chandrakala A Narasimhulu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Death ◽  
Membrane Damage ◽  
Final Concentration ◽  
Bone Marrow Stem Cells ◽  
Cell Membrane Damage ◽  
Cell Based Therapy

Aims: cell-based therapy with bone marrow stem cells (MSCs) remains a viable option for tissue repair and regeneration. One of the major challenges for cell-based therapy is the limited survival of the cells after in vivo administration. The exact mechanism(s) for impaired in vivo survival of the implanted MSCs remains to be defined. Oxidized low-density lipid protein (ox-LDL) is a natural product in human blood, and the major contributor to the development of atherosclerosis. The present study was to investigate the effect of ox-LDL on the survival of bone marrow stem cells and the mechanisms in vitro. Methods and Results: Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox-LDL (with the final concentration of 10 and 20 ug/ml) for up to 48 hours. Exposure to ox-LDL resulted in significant cell death and apoptosis of MAPCs in association with a significant increase in LDH release in the conditioned media in a dose- and time-dependent manner, indicating significant cell membrane damage. The membrane damage was further confirmed with the rapid entry of the small fluorescent dye FM1-43 as detected using confocal microscope. Ox-LDL generated a significant amount of reactive oxygen species (ROS) in the culture system as measured with electron paramagnetic resonance spectroscopy. The antioxidant N-acetylcysteine (NAC, 0.1 mM) completely inhibited the production of ROS from ox-LDL. However, it didn’t prevent ox-LDL-induced cell death or apoptosis. However, pre-treatment of the cells with the specific membrane protective recombinant human MG53 protein (rhMG53)(66 ug/ml, final concentration) significantly, reduced LDH release and the entry of FM1-43 dye into the cells exposed to ox-LDL. Conclusion: Ox-LDL enhanced cell death and apoptosis of MAPCs with a mechanism independent of ROS generation in vitro. Ox-LDL impaired the survival of MAPCs partially through cell membrane damage in vitro.

Abstract 8: GTPase-Activating Protein for Rho Associated with FAK (GRAF) Regulates Cardiomyocyte Membrane Integrity

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Thomas J O'Neill ◽  
Kaitlin Lenhart ◽  
Jason Doherty ◽  
Mauricio Rojas ◽  
Mack P Christopher ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Muscle Pathology ◽  
Blue Dye ◽  
Membrane Repair ◽  
Cell Membrane Damage ◽  
Deficient Mice

Cardiac myocytes are unique in their requirement to sustain continuous repetitive contraction in the setting of intense mechanical stress while simultaneously maintaining high membrane integrity for an appropriate electrical gradient. The consequence of failure of the membrane repair response has been highlighted in recent reports linking cardiomyocyte membrane fragility with cardiac degeneration in patients as well as in their analogous mouse models. Herein, we describe a novel role for GTPase activator for Rho associated with Focal Adhesion Kinase (GRAF) in regulating cardiomyocyte membrane integrity. We previously published that disruption of GRAF in Xenopus laevis resulted in progressive skeletal muscle degeneration. We now show that GRAF-depleted tadpoles exhibit defective cardiac formation and function. Interestingly, damage of muscle cells in vivo and in vitro led to a translocation of GRAF to the sarcolemma, suggesting that GRAF may be an important component of the cardiac membrane repair machinery. To further explore this possibility, we generated GRAF hypomorphic mice that exhibit greater than 99% reduction of endogenous GRAF expression. While GRAF deficient mice show normal Mendelian birth distribution and are viable, they exhibit a modest skeletal muscle pathology. Although baseline cardiac integrity was not compromised in GRAF deficient mice, treatment either with cardiotoxin or intraperitoneal injection of isoproterenol led to elevated cardiomyocyte membrane damage (assessed by Evan’s blue dye uptake) in GRAF deficient compared to control mice (19% vs 2% of myocytes within afflicted ventricular area for cardiotoxin, 18% vs 8% for isoproterenol respectively). Moreover, cultured GRAF null myocytes exhibited a significantly attenuated membrane resealing response following laser-mediated disruption compared to GRAF-containing control cells as assessed by accumulation of the membrane impermeable dye, FM-143. As well, the survival rate after injury of GRAF-deficient cells was markedly attenuated (20% vs 85% in control cells). While cardiac cell membrane damage is likely a frequent and important event, the repair process is currently understudied, and this is the first report to implicate a Rho regulator in this response.

scholarly journals Addition of Ceftaroline to Daptomycin after Emergence of Daptomycin-Nonsusceptible Staphylococcus aureus during Therapy Improves Antibacterial Activity

2012 ◽  
Vol 56 (10) ◽  
pp. 5296-5302 ◽  
Author(s):  
Warren E. Rose ◽  
Lucas T. Schulz ◽  
David Andes ◽  
Rob Striker ◽  
Andrew D. Berti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Membrane Damage ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Content Type ◽  
Cell Membrane Damage

ABSTRACTAntistaphylococcal beta-lactams enhance daptomycin activity and have been used successfully in combination for refractory methicillin-resistantStaphylococcus aureus(MRSA) infections. Ceftaroline possesses MRSA activity, but it is unknown if it improves the daptomycin potency comparably to other beta-lactams. We report a complex patient case of endocarditis who was treated with daptomycin in combination with ceftaroline, which resulted in clearance of a daptomycin-nonsusceptible strain. Anin vitropharmacokinetic/pharmacodynamic model of renal failure was used to simulate the development of daptomycin resistance and evaluate the microbiologic effects of daptomycin plus ceftaroline treatment. Combination therapy with daptomycin and ceftaroline restored daptomycin sensitivityin vivoand resulted in clearance of persistent blood cultures. Daptomycin susceptibilityin vitrowas increased in the presence of either ceftaroline or oxacillin. Daptomycin at 6 mg/kg of body weight every 48 h was bactericidal in the model but resulted in regrowth and daptomycin resistance (MIC, 2 to 4 μg/ml) with continued monotherapy. The addition of ceftaroline at 200 mg every 12 h after the emergence of daptomycin resistance enhanced bacterial killing. Importantly, daptomycin plus ceftaroline as the initial combination therapy produced rapid and sustained bactericidal activity and prevented daptomycin resistance. Bothin vivo- andin vitro-derived daptomycin resistance resulted in bacteria with more fluid cell membranes. After ceftaroline was added in the model, fluidity was restored to the level of the initialin vivoisolate. Daptomycin-resistant isolates required high daptomycin exposures (at least 10 mg/kg) to optimize cell membrane damage with daptomycin alone. Ceftaroline combined with daptomycin was effective in eliminating daptomycin-resistant MRSA, and these results further justify the potential use of daptomycin plus beta-lactam therapy for these refractory infections.

scholarly journals Application of Quantum Dots in Biological Imaging

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Shan Jin ◽  
Yanxi Hu ◽  
Zhanjun Gu ◽  
Lei Liu ◽  
Hai-Chen Wu
Keyword(s):  
Quantum Dots ◽  
Organic Dyes ◽  
Rapid Development ◽  
Emission Spectra ◽  
Major Type ◽  
Biological Applications ◽  
Biological Studies ◽  
Polymer Dots

Quantum dots (QDs) are a group of semiconducting nanomaterials with unique optical and electronic properties. They have distinct advantages over traditional fluorescent organic dyes in chemical and biological studies in terms of tunable emission spectra, signal brightness, photostability, and so forth. Currently, the major type of QDs is the heavy metal-containing II-IV, IV-VI, or III-V QDs. Silicon QDs and conjugated polymer dots have also been developed in order to lower the potential toxicity of the fluorescent probes for biological applications. Aqueous solubility is the common problem for all types of QDs when they are employed in the biological researches, such asin vitroandin vivoimaging. To circumvent this problem, ligand exchange and polymer coating are proven to be effective, besides synthesizing QDs in aqueous solutions directly. However, toxicity is another big concern especially forin vivostudies. Ligand protection and core/shell structure can partly solve this problem. With the rapid development of QDs research, new elements and new morphologies have been introduced to this area to fabricate more safe and efficient QDs for biological applications.

scholarly journals Nanohole-boosted electron transport between nanomaterials and bacteria as a concept for nano–bio interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tonglei Shi ◽  
Xuan Hou ◽  
Shuqing Guo ◽  
Lei Zhang ◽  
Changhong Wei ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Electron Transport ◽  
Bacterial Infection ◽  
Membrane Damage ◽  
Extracellular Dna ◽  
High Electron ◽  
Cell Membrane Damage ◽  
Antibiotic Drug

AbstractBiofilms contribute to bacterial infection and drug resistance and are a serious threat to global human health. Antibacterial nanomaterials have attracted considerable attention, but the inhibition of biofilms remains a major challenge. Herein, we propose a nanohole-boosted electron transport (NBET) antibiofilm concept. Unlike known antibacterial mechanisms (e.g., reactive oxygen species production and cell membrane damage), nanoholes with atomic vacancies and biofilms serve as electronic donors and receptors, respectively, and thus boost the high electron transport capacity between nanomaterials and biofilms. Electron transport effectively destroys the critical components (proteins, intercellularly adhered polysaccharides and extracellular DNA) of biofilms, and the nanoholes also significantly downregulate the expression of genes related to biofilm formation. The anti-infection capacity is thoroughly verified both in vitro (human cells) and in vivo (rat ocular and mouse intestinal infection models), and the nanohole-enabled nanomaterials are found to be highly biocompatible. Importantly, compared with typical antibiotics, nanomaterials are nonresistant and thereby exhibit high potential for use in various applications. As a proof-of-principle demonstration, these findings hold promise for the use of NBET in treatments for pathogenic bacterial infection and antibiotic drug resistance.

scholarly journals Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity

2020 ◽  
Vol 6 (3) ◽  
pp. 153
Author(s):  
Géssica Andrade ◽  
Haniel Orlando ◽  
Liliana Scorzoni ◽  
Reginaldo Pedroso ◽  
Fariza Abrão ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Membrane Damage ◽  
Antimicrobial Properties ◽  
Leaf Extracts ◽  
Cell Membrane Damage ◽  
C Elegans ◽  
Cellular Target

Plants belonging to the genus Copaifera are widely used in Brazil due to their antimicrobial properties, among others. The re-emergence of classic fungal diseases as a consequence of antifungal resistance to available drugs has stimulated the search for plant-based compounds with antifungal activity, especially against Candida. The Candida-infected Caenorhabditis elegans model was used to evaluate the in vitro antifungal potential of Copaifera leaf extracts and trunk oleoresins against Candida species. The Copaifera leaf extracts exhibited good antifungal activity against all Candida species, with MIC values ranging from 5.86 to 93.75 µg/mL. Both the Copaifera paupera and Copaifera reticulata leaf extracts at 46.87 µg/mL inhibited Candida glabrata biofilm formation and showed no toxicity to C. elegans. The survival of C. glabrata-infected nematodes increased at all the tested extract concentrations. Exposure to Copaifera leaf extracts markedly increased C. glabrata cell vacuolization and cell membrane damage. Therefore, Copaifera leaf extracts are potential candidates for the development of new and safe antifungal agents.

scholarly journals In VitroCytotoxicity andIn VivoAcute and Chronic Toxicity of Xanthii Fructus and Its Processed Product

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yu ◽  
Mei-Zhen Song ◽  
Jing Wang ◽  
Yun-Fei Li ◽  
Pei Lin ◽  
...  
Keyword(s):  
Chronic Toxicity ◽  
Membrane Damage ◽  
Male Rats ◽  
Pathological Examination ◽  
Group V ◽  
Cell Membrane Damage ◽  
Nasal Disease ◽  
Liver And Kidney

Xanthii Fructus (XF), the fruit ofXanthium sibiricumPatr., was used in the treatment of rhinitis and related nasal disease. Adverse effects of Xanthii Fructus are frequently reported these years. In the paper,in vitrorenal cytotoxicity andin vivoacute and chronic toxicity researches of Xanthii Fructus (XF) and its processed product (processed Xanthii Fructus (PXF)) were carried out. Water extraction of XF displayed no cell membrane damage effects even in the highest concentration (100 μg/mL); however, it might affect the function of renal cell mitochondria. Acute toxicities were observed only in high and middle dosage groups. Fortunately, the single dose administration of XF or PXF was safe even at the highest daily dosage. Twelve-week chronic toxicity assays were performed in SD rats with low, middle, and high dosage. Notable changes in body weight and blood cell and BUN and Scr changes sporadically occurred in middle and high groups after the 9th week. Serum HA and HPCIII values were sustained increasing from the 4th week to the 8th week in Group V male rats, which indicated that the renal fibrosis risks still existed although no fibrosis was found in the pathological examination of the liver and kidney.

scholarly journals Low-dose Exposure to Black Carbon and Cadmium Significantly Induce Lung Injury by Promoting Cellular Apoptosis

2021 ◽  
Author(s):  
Lingjuan Wang ◽  
Shanyu Bao ◽  
Xiaolong Liu ◽  
Fan Wang ◽  
Jinwei Zhang ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Biological Effects ◽  
Membrane Damage ◽  
The Body ◽  
Cell Membrane Damage ◽  
Induce Lung Injury ◽  
Cellular Apoptosis ◽  
Cd Exposure

Abstract PMs has adverse biological effects on major living organs in the body, including lungs. The complex composition of PM2.5, including carbon black and heavy metals, cause toxic effects to the lung. The synergistic effects of CB and Cd were less investigated in previous study. In our research, we deciphered the combination of CBs and Cd enhanced the cytotoxicity in BEAS-2B cells in vitro and in vivo. In the molecular level, the intracellular level of Cd increased, as a result of the cell membrane damage, causing high expression of MT-1 in BEAS-2B cells. Moreover, the expression of BAX increased, and the expression of BCL-2 decreased. Collectively, our data suggests the apoptosis effect of synergistic effects of CB and Cd exposure.

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