22 research outputs found

    Electrodeformation-Based Biomechanical Chip for Quantifying Global Viscoelasticity of Cancer Cells Regulated by Cell Cycle

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    Mechanical phenotypes of cells are found to hold vital clues to reveal cellular functions and behaviors, which not only has great physiological significance but also is crucial for disease diagnosis. To this end, we developed a set of electrodeformation-based biomechanical microchip assays to quantify mechanical phenotypes on the single-cell level. By investigating the spatiotemporal dynamics of cancer cells driven by dielectrophoresis forces, we captured the key global viscoelastic indexes including cellular elasticity, viscosity, and transition time that was defined as the ratio of the transient viscosity and elasticity, simultaneously, and thus explored their intrinsic correlation with cell cycle progression. Our results showed that both global elasticity and viscosity have a significant periodic variation with cell cycle progression, but the transition time remained unchanged in the process, indicating that it might be an intrinsic property of cancer cells that is independent of the cell cycle and the type of cell in the experiments. Further, we investigated the molecular mechanism regulating cellular viscoelastic phenotypes on the biomechanical chips through intracellular cytoskeletal perturbation assays. These findings, together with the electrodeformation-based microchip technique, not only reveal the relation between mechanical phenotypes of cancer cells and cell cycle progression but also provide a platform for implementing multi-index mechanical phenotype assays associated with cancer cell cycles in the clinic

    Presentation_1_Mucoid Acinetobacter baumannii enhances anti-phagocytosis through reducing C3b deposition.pdf

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    BackgroundMultidrug resistant (MDR) Acinetobacter baumannii causes serious infections in intensive care units and is hard to be eradicated by antibiotics. Many A. baumannii isolates are identified as the mucoid type recently, but the biological characteristics of mucoid A. baumannii and their interactions with host cells remains unclear.MethodsThe mucoid phenotype, antimicrobial susceptibility, biofilm-forming ability, acid resistance ability, peroxide tolerance, and in vivo toxicity of clinical ICUs derived A. baumannii isolates were first investigated. Secondly, the phagocytic resistance and invasive capacity of A. baumannii isolates to macrophages (MH-S, RAW264.7) and epithelial cells (A549) were analyzed. Furthermore, the abundance of C3b (complement factor C3 degradation product) deposition on the surface of A. baumannii was investigated. Last, the relationship between C3b deposition and the abundance of capsule in A. baumannii isolates were analyzed.ResultsThese A. baumannii strains showed different mucoid phenotypes including hyper mucoid (HM), medium mucoid (MM), and low mucoid (LM). All tested strains were MDR with high tolerance to either acid or hydrogen peroxide exposure. Notably, these mucoid strains showed the increase of mortality in the Galleria mellonella infection models. Besides, the HM strain exhibited less biofilm abundance, higher molecular weight (MW) of capsule, and greater anti-phagocytic activity to macrophages than the LM strain. Together with the increased abundance of capsule, high expression of tuf gene (associated with the hydrolysis of C3b), the HM strain effectively inhibits C3b deposition on bacterial surface, resulting in the low-opsonization phenotype.ConclusionCapsular characteristics facilitate the anti-phagocytic activity in hyper mucoid A. baumannii through the reduction of C3b deposition. Mucoid A. baumannii exhibits high phagocytosis resistance to both macrophages and epithelial cells.</p

    Milk Exosomes Facilitate Oral Delivery of Drugs against Intestinal Bacterial Infections

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    Biopharmaceutics Classification System (BCS) class II and IV drugs exhibit low solubility and suffer a limitation in oral administration. Exosomes have attracted intensive attention in the efficient delivery of such compounds. However, low gastrointestinal stability and high production cost of exosomes hinder their development as drug carriers. Here, milk exosomes are functionalized with phosphatidylserine and are capable of improving the solubility of BCS class II and IV drugs, resulting in facilitating the oral delivery of the drugs. A natural flavonoid, α-mangostin, is loaded into exosomes (AExo) to enhance the antibacterial efficiency, demonstrated by clearing 99% of bacteria in macrophages. Furthermore, AExo exhibits high mucus penetrability and shows a significant therapeutic efficacy in two animal infection models. Collectively, this work expands the application of exosomes from bovine milk with simple operation and low cost, shedding light on the potential of milk exosomes in improving the solubility of drugs to enhance the efficacy of oral administration

    Characteristics of included studies about the four VDR polymorphisms and coronary artery disease.

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    Characteristics of included studies about the four VDR polymorphisms and coronary artery disease.</p

    The potential function of the VDR polymorphisms predicted by SNPinfo.

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    The potential function of the VDR polymorphisms predicted by SNPinfo.</p

    Complex Formation between NheB and NheC Is Necessary to Induce Cytotoxic Activity by the Three-Component <i>Bacillus cereus</i> Nhe Enterotoxin

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    <div><p>The nonhemolytic enterotoxin (Nhe) is known as a major pathogenicity factor for the diarrheal type of food poisoning caused by <i>Bacillus cereus.</i> The Nhe complex consists of NheA, NheB and NheC, all of them required to reach maximum cytotoxicity following a specific binding order on cell membranes. Here we show that complexes, formed between NheB and NheC under natural conditions before targeting the host cells, are essential for toxicity in Vero cells. To enable detection of NheC and its interaction with NheB, monoclonal antibodies against NheC were established and characterized. The antibodies allowed detection of recombinant NheC in a sandwich immunoassay at levels below 10 ng ml<sup>−1</sup>, but no or only minor amounts of NheC were detectable in natural culture supernatants of <i>B. cereus</i> strains. When NheB- and NheC-specific monoclonal antibodies were combined in a sandwich immunoassay, complexes between NheB and NheC could be demonstrated. The level of these complexes was directly correlated with the relative concentrations of NheB and NheC. Toxicity, however, showed a bell-shaped dose-response curve with a plateau at ratios of NheB and NheC between 50:1 and 5:1. Both lower and higher ratios between NheB and NheC strongly reduced cytotoxicity. When the ratio approached an equimolar ratio, complex formation reached its maximum resulting in decreased binding of NheB to Vero cells. These data indicate that a defined level of NheB-NheC complexes as well as a sufficient amount of free NheB is necessary for efficient cell binding and toxicity. Altogether, the results of this study provide evidence that the interaction of NheB and NheC is a balanced process, necessary to induce, but also able to limit the toxic action of Nhe.</p></div

    The Begg’s plot of Publication bias for the VDR polymorphism.

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    A: rs2228570 polymorphism; B: rs1544410 polymorphism; C: rs731236 polymorphism; D: rs7975232 polymorphism. CAD = Coronary artery disease, VDR = vitamin D receptor, OR = odd ration, CI = confidence interval.</p

    The RNAfold structure analysis of the VDR rs1544410 polymorphism.

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    A: rs2228570 polymorphism; B: rs731236 polymorphism. VDR = vitamin D receptor.</p
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