ResearchPad - Bioengineering https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice]]> https://www.researchpad.co/product?articleinfo=N69d6ab98-bd8d-4010-844a-59b94990e522

Introduction

Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting.

Methods

Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice.

Results

In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology.

Conclusion

Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.

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<![CDATA[Targeted Prodrug-Based Self-Assembled Nanoparticles for Cancer Therapy]]> https://www.researchpad.co/product?articleinfo=N2b0f5f7d-d5ab-49b6-9010-39c3b297e587

Background

Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic.

Methods and Results

In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects.

Conclusion

This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future.

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<![CDATA[Enzymatic Synthesis of Ricinoleyl Hydroxamic Acid Based on Commercial Castor Oil, Cytotoxicity Properties and Application as a New Anticancer Agent]]> https://www.researchpad.co/product?articleinfo=N2ee31eb3-084a-41f9-bd1c-0b276d684b2d

Background

New anticancer agents that rely on natural/healthy, not synthetic/toxic, components are very much needed.

Methods

Ricinoleyl hydroxamic acid (RHA) was synthesized from castor oil and hydroxylamine using Lipozyme TL IM as a catalyst. To optimize the conversion, the effects of the following parameters were investigated: type of organic solvent, period of reaction, amount of enzyme, the molar ratio of reactants and temperature. The highest conversion was obtained when the reaction was carried out under the following conditions: hexane as a solvent; reaction period of 48 hours; 120 mg of Lipozyme TL IM/3 mmol oil; HA-oil ratio of 19 mmol HA/3 mmol oil; and temperature of 40°C. The cytotoxicity of the synthesized RHA was assessed using human dermal fibroblasts (HDF), and its application towards fighting cancer was assessed using melanoma and glioblastoma cancer cells over a duration of 24 and 48 hours.

Results

RHA was successfully synthesized  and it demonstrated strong anticancer activity against glioblastoma and melanoma cells at as low as a 1 µg/mL concentration while it did not demonstrate any toxicity against HDF cells.

Conclusion

This is the first report on the synthesis of RHA with great potential to be used as a new anticancer agent.

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<![CDATA[Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy]]> https://www.researchpad.co/product?articleinfo=N0333ac7a-c329-4c80-b402-750b5176061b

Purpose

Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.

Methods

The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.

Results

The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.

Conclusion

Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.

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<![CDATA[Tissue Engineering Using Vascular Organoids From Human Pluripotent Stem Cell Derived Mural Cell Phenotypes]]> https://www.researchpad.co/product?articleinfo=Nf13c55b4-2868-4ed9-89da-fb472063def6

Diffusion is a limiting factor in regenerating large tissues (100–200 μm) due to reduced nutrient supply and waste removal leading to low viability of the regenerating cells as neovascularization of the implant by the host is a slow process. Thus, generating prevascularized tissue engineered constructs, in which endothelial (ECs) and mural (MCs) cells, such as smooth muscle cells (SMCs), and pericytes (PCs), are preassembled into functional in vitro vessels capable of rapidly connecting to the host vasculature could overcome this obstacle. Toward this purpose, using feeder-free and low serum conditions, we developed a simple, efficient and rapid in vitro approach to induce the differentiation of human pluripotent stem cells-hPSCs (human embryonic stem cells and human induced pluripotent stem cells) to defined SMC populations (contractile and synthetic hPSC-SMCs) by extensively characterizing the cellular phenotype (expression of CD44, CD73, CD105, NG2, PDGFRβ, and contractile proteins) and function of hPSC-SMCs. The latter were phenotypically and functionally stable for at least 8 passages, and could stabilize vessel formation and inhibit vessel network regression, when co-cultured with ECs in vitro. Subsequently, using a methylcellulose-based hydrogel system, we generated spheroids consisting of EC/hPSC-SMC (vascular organoids), which were extensively phenotypically characterized. Moreover, the vascular organoids served as focal starting points for the sprouting of capillary-like structures in vitro, whereas their delivery in vivo led to rapid generation of a complex functional vascular network. Finally, we investigated the vascularization potential of these vascular organoids, when embedded in hydrogels composed of defined extracellular components (collagen/fibrinogen/fibronectin) that can be used as scaffolds in tissue engineering applications. In summary, we developed a robust method for the generation of defined SMC phenotypes from hPSCs. Fabrication of vascularized tissue constructs using hPSC-SMC/EC vascular organoids embedded in chemically defined matrices is a significant step forward in tissue engineering and regenerative medicine.

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<![CDATA[Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc]]> https://www.researchpad.co/product?articleinfo=N96062283-4421-4f07-8486-ec0c1acc7b4d

Extracellular vesicles (EVs) are lipid membrane particles carrying proteins, lipids, DNA, and various types of RNA that are involved in intercellular communication. EVs derived from mesenchymal stem cells (MSCs) have been investigated extensively in many different fields due to their crucial role as regeneration drivers, but research for their use in degenerative diseases of the intervertebral disc (IVD) has only started recently. MSC-derived EVs not only promote extracellular matrix synthesis and proliferation in IVD cells, but also reduce apoptosis and inflammation, hence having multifunctional beneficial effects that seem to be mediated by specific miRNAs (such as miR-233 and miR-21) within the EVs. Aside from MSC-derived EVs, IVD-derived EVs (e.g., stemming from notochordal cells) also have important functions in IVD health and disease. This article will summarize the current knowledge on MSC-derived and IVD-derived EVs and will highlight areas of future research, including the isolation and analysis of EV subpopulations or exposure of MSCs to cues that may enhance the therapeutic potential of released EVs.

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<![CDATA[Gene Editing Regulation and Innovation Economics]]> https://www.researchpad.co/product?articleinfo=Na9b0e3e9-b736-41c0-b802-b8dc3a213d39

Argentina was the first country that enacted regulatory criteria to assess if organisms resulting from new breeding techniques (NBTs) are to be regarded as genetically modified organisms (GMOs) or not. The country has now accumulated 4 year of experience applying such criteria, reaching a considerable number of cases, composed mostly of gene-edited plants, animals, and microorganisms of agricultural use. This article explores the effects on economic innovation of such regulatory experience. This is done by comparing the cases of products derived from gene editing and other NBTs that have been presented to the regulatory system, against the cases of GMOs that have been deregulated in the country. Albeit preliminary, this analysis suggests that products from gene editing will have different profiles and market release rates compared with the first wave of products from the so called “modern biotechnology.” Gene editing products seems to follow a much faster development rate from bench to market. Such development is driven by a more diverse group of developers, and led mostly by small and medium enterprises (SMEs) and public research institutions. In addition, product profiles are also more diversified in terms of traits and organisms. The inferences of these findings for the agricultural and biotechnology sectors, particularly in developing countries, are discussed.

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<![CDATA[Synthetic Biology Tools for Genome and Transcriptome Engineering of Solventogenic Clostridium]]> https://www.researchpad.co/product?articleinfo=N64df6521-f3a0-47bc-86eb-824714de9ad4

Strains of Clostridium genus are used for production of various value-added products including fuels and chemicals. Development of any commercially viable production process requires a combination of both strain and fermentation process development strategies. The strain development in Clostridium sp. could be achieved by random mutagenesis, and targeted gene alteration methods. However, strain improvement in Clostridium sp. by targeted gene alteration method was challenging due to the lack of efficient tools for genome and transcriptome engineering in this organism. Recently, various synthetic biology tools have been developed to facilitate the strain engineering of solventogenic Clostridium. In this review, we consolidated the recent advancements in toolbox development for genome and transcriptome engineering in solventogenic Clostridium. Here we reviewed the genome-engineering tools employing mobile group II intron, pyrE alleles exchange, and CRISPR/Cas9 with their application for strain development of Clostridium sp. Next, transcriptome engineering tools such as untranslated region (UTR) engineering and synthetic sRNA techniques were also discussed in context of Clostridium strain engineering. Application of any of these discussed techniques will facilitate the metabolic engineering of clostridia for development of improved strains with respect to requisite functional attributes. This might lead to the development of an economically viable butanol production process with improved titer, yield and productivity.

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<![CDATA[Predicting Knee Joint Instability Using a Tibio-Femoral Statistical Shape Model]]> https://www.researchpad.co/product?articleinfo=Ncfa0bac3-6ba9-4eae-8689-54452b8ef41e

Statistical shape models (SSMs) are a well established computational technique to represent the morphological variability spread in a set of matching surfaces by means of compact descriptive quantities, traditionally called “modes of variation” (MoVs). SSMs of bony surfaces have been proposed in biomechanics and orthopedic clinics to investigate the relation between bone shape and joint biomechanics. In this work, an SSM of the tibio-femoral joint has been developed to elucidate the relation between MoVs and bone angular deformities causing knee instability. The SSM was built using 99 bony shapes (distal femur and proximal tibia surfaces obtained from segmented CT scans) of osteoarthritic patients. Hip-knee-ankle (HKA) angle, femoral varus-valgus (FVV) angle, internal-external femoral rotation (IER), tibial varus-valgus (TVV) angles, and tibial slope (TS) were available across the patient set. Discriminant analysis (DA) and logistic regression (LR) classifiers were adopted to underline specific MoVs accounting for knee instability. First, it was found that thirty-four MoVs were enough to describe 95% of the shape variability in the dataset. The most relevant MoVs were the one encoding the height of the femoral and tibial shafts (MoV #2) and the one representing variations of the axial section of the femoral shaft and its bending in the frontal plane (MoV #5). Second, using quadratic DA, the sensitivity results of the classification were very accurate, being all >0.85 (HKA: 0.96, FVV: 0.99, IER: 0.88, TVV: 1, TS: 0.87). The results of the LR classifier were mostly in agreement with DA, confirming statistical significance for MoV #2 (p = 0.02) in correspondence to IER and MoV #5 in correspondence to HKA (p = 0.0001), FVV (p = 0.001), and TS (p = 0.02). We can argue that the SSM successfully identified specific MoVs encoding ranges of alignment variability between distal femur and proximal tibia. This discloses the opportunity to use the SSM to predict potential misalignment in the knee for a new patient by processing the bone shapes, removing the need for measuring clinical landmarks as the rotation centers and mechanical axes.

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<![CDATA[Omics-Based Mechanistic Insight Into the Role of Bioengineered Nanoparticles for Biotic Stress Amelioration by Modulating Plant Metabolic Pathways]]> https://www.researchpad.co/product?articleinfo=Ndebac4f8-aaad-4d54-b214-925b3f7af1c4

Bioengineered silver nanoparticles can emerge as a facile approach to combat plant pathogen, reducing the use of pesticides in an eco-friendly manner. The plants’ response during tripartite interaction of plant, pathogen, and nanoparticles remains largely unknown. This study demonstrated the use of bioengineered silver nanoparticles in combating black spot disease caused by necrotrophic fungus Alternaria brassicicola in Arabidopsis thaliana via foliar spray. The particles reduced disease severity by 70–80% at 5 μg/ml without showing phytotoxicity. It elicited plant immunity by a significant reduction in reactive oxygen species (ROS), decreases in stress enzymes by 0.6–19.8-fold, and emergence of autophagy. Comparative plant proteomics revealed 599 proteins expressed during the interaction, where 117 differential proteins were identified. Among different categories, proteins involved in bioenergy and metabolism were most abundant (44%), followed by proteins involved in plant defense (20%). Metabolic profiling by gas chromatography–mass spectroscopy yielded 39 metabolite derivatives in non-polar fraction and 25 in the polar fraction of plant extracts. It was observed that proteins involved in protein biogenesis and early plant defense were overexpressed to produce abundant antimicrobial metabolites and minimize ROS production. Bioengineered silver nanoparticles performed dual functions to combat pathogen attack by killing plant pathogen and eliciting immunity by altering plant defense proteome and metabolome.

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<![CDATA[Angiogenic Potential of Tissue Engineered Cartilage From Human Mesenchymal Stem Cells Is Modulated by Indian Hedgehog and Serpin E1]]> https://www.researchpad.co/product?articleinfo=N7724652d-cff7-43f6-bae5-39cc31469fe5

With rising demand for cartilage tissue repair and replacement, the differentiation of mesenchymal stem cells (BMSCs) into cartilage tissue forming cells provides a promising solution. Often, the BMSC-derived cartilage does not remain stable and continues maturing to bone through the process of endochondral ossification in vivo. Similar to the growth plate, invasion of blood vessels is an early hallmark of endochondral ossification and a necessary step for completion of ossification. This invasion originates from preexisting vessels that expand via angiogenesis, induced by secreted factors produced by the cartilage graft. In this study, we aimed to identify factors secreted by chondrogenically differentiated bone marrow-derived human BMSCs to modulate angiogenesis. The secretome of chondrogenic pellets at day 21 of the differentiation program was collected and tested for angiogenic capacity using in vitro endothelial migration and proliferation assays as well as the chick chorioallantoic membrane (CAM) assay. Taken together, these assays confirmed the pro-angiogenic potential of the secretome. Putative secreted angiogenic factors present in this medium were identified by comparative global transcriptome analysis between murine growth plate cartilage, human chondrogenic BMSC pellets and human neonatal articular cartilage. We then verified by PCR eight candidate angiogenesis modulating factors secreted by differentiated BMSCs. Among those, Serpin E1 and Indian Hedgehog (IHH) had a higher level of expression in BMSC-derived cartilage compared to articular chondrocyte derived cartilage. To understand the role of these factors in the pro-angiogenic secretome, we used neutralizing antibodies to functionally block them in the conditioned medium. Here, we observed a 1.4-fold increase of endothelial cell proliferation when blocking IHH and 1.5-fold by Serpin E1 blocking compared to unblocked control conditioned medium. Furthermore, endothelial migration was increased 1.9-fold by Serpin E1 blocking and 2.7-fold by IHH blocking. This suggests that the pro-angiogenic potential of chondrogenically differentiated BMSC secretome could be further augmented through inhibition of specific factors such as IHH and Serpin E1 identified as anti-angiogenic factors.

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<![CDATA[Untangling Photofaradaic and Photocapacitive Effects in Organic Optoelectronic Stimulation Devices]]> https://www.researchpad.co/product?articleinfo=N38990c17-9210-486b-8d70-7356b1d8831b

Light, as a versatile and non-invasive means to elicit a physiological response, offers solutions to problems in basic research as well as in biomedical technologies. The complexity and limitations of optogenetic methods motivate research and development of optoelectronic alternatives. A recently growing subset of approaches relies on organic semiconductors as the active light absorber. Organic semiconductors stand out due to their high optical absorbance coefficients, mechanical flexibility, ability to operate in a wet environment, and potential biocompatibility. They could enable ultrathin and minimally invasive form factors not accessible with traditional inorganic materials. Organic semiconductors, upon photoexcitation in an aqueous medium, can transduce light into (1) photothermal heating, (2) photochemical/photocatalytic redox reactions, (3) photocapacitive charging of electrolytic double layers, and (4) photofaradaic reactions. In realistic conditions, different effects may coexist, and understanding their role in observed physiological phenomena is an area of critical interest. This article serves to evaluate the emerging picture of photofaradaic vs. photocapacitive effects in the context of our group’s research efforts and that of others over the past few years. We present simple experiments which can be used to benchmark organic optoelectronic stimulation devices.

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<![CDATA[Significantly Enhanced Synthesis of Aromatic Esters of Arbutin Catalyzed by Immobilized Lipase in Co-solvent Systems]]> https://www.researchpad.co/product?articleinfo=N74bfa51e-691c-42a3-8bc3-baf84d054e3e

Highly efficient and regioselective synthesis of pharmacologically interesting aromatic esters of arbutin catalyzed by immobilized lipase from Penicillium expansum in co-solvent systems was successfully carried out. As compared to tetrahydrofuran solvent, the initial rate and substrate conversion of arbutin vanilylation were markedly enhanced in tetrahydrofuran-isopropyl ether (20%, v/v). Moreover, the effects of three reaction parameters (enzyme amount, temperature and substrate molar ratio of vinyl vanillic acid to arbutin) on 6′-O-vanilloyl-arbutin synthesis were scrutinized and the key process parameters were optimized using response surface methodology (RSM). The experimental data were fitted well to a second order polynomial model by using multiple regression analysis. The best combination of variables was 50°C, 93 U/mL and 11 for the reaction temperature, the enzyme amount and mole ratio of arbutin to vinyl vanilic acid, respectively, and which the reaction rate, substrate conversion and regioselectivity were as high as 8.2 mM/h, 93 and 99%. It was worth noting that a variety of aromatic esters of arbutin were obtained with much higher conversion (93–99%) at these optimal conditions.

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<![CDATA[Promoting Cardiac Regeneration and Repair Using Acellular Biomaterials]]> https://www.researchpad.co/product?articleinfo=Ne63a6795-bdfc-46dd-98f2-01a385ca0b6e

Ischemic heart disease is a common cause of end-stage heart failure and has persisted as one of the main causes of end stage heart failure requiring transplantation. Maladaptive myocardial remodeling due to ischemic injury involves multiple cell types and physiologic mechanisms. Pathogenic post-infarct remodeling involves collagen deposition, chamber dilatation and ventricular dysfunction. There have been significant improvements in medication and revascularization strategies. However, despite medical optimization and opportunities to restore blood flow, physicians lack therapies that directly access and manipulate the heart to promote healthy post-infarct myocardial remodeling. Strategies are now arising that use bioactive materials to promote cardiac regeneration by promoting angiogenesis and inhibiting cardiac fibrosis; and many of these strategies leverage the unique advantage of cardiac surgery to directly visualize and manipulate the heart. Although cellular-based strategies are emerging, multiple barriers exist for clinical translation. Acellular materials have also demonstrated preclinical therapeutic potential to promote angiogenesis and attenuate fibrosis and may be able to surmount these translational barriers. Within this review we outline various acellular biomaterials and we define epicardial infarct repair and intramyocardial injection, which focus on administering bioactive materials to the cardiac epicardium and myocardium respectively to promote cardiac regeneration. In conjunction with optimized medical therapy and revascularization, these techniques show promise to upregulate pathways of cardiac regeneration to preserve heart function.

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<![CDATA[Pulsed Electric Field Extraction of α and β-Acids From Pellets of Humulus lupulus (Hop)]]> https://www.researchpad.co/product?articleinfo=N41358386-3c36-4762-8ff6-7938e5bbbc86

This paper investigates the process of extracting hop pellets (hops) utilizing the pulsed electric field (PEF) technique and the contrasting effects of the technique between two distinct hop varieties (one bitter and one aromatic). The effect of PEF on the extraction was evaluated by measuring the concentration of α-acids and β-acids (humulones and lupulones). Regarding the aromatic character, the hop’s volatile caryophyllene, humulene and β-myrcene were analyzed both with and without employing the PEF treatment. In order to analyze the acids and the volatile fraction, the analytical method of UV–vis spectrophotometry was applied followed by gas chromatography coupled with mass spectrometry. For the second technique, the extracts were previously purified through a Graphitized Carbon Black syringe for Solid Phase Extraction. The results revealed that PEF had a positive impact on the alpha acids of bitter hops by increasing the extraction rate of these acids by 20%, while the volatiles demonstrated an increase of 5.6 and 7.4% for humulene and caryophyllene, respectively. Concerning the aromatic variety of hops, the PEF treatment appeared to have no noteworthy effects.

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<![CDATA[Nanoparticles as Versatile Tools for Mechanotransduction in Tissues and Organoids]]> https://www.researchpad.co/product?articleinfo=N8182eb3e-e887-4f08-a3e4-5e52834b3481

Organoids are 3D multicellular constructs that rely on self-organized cell differentiation, patterning and morphogenesis to recapitulate key features of the form and function of tissues and organs of interest. Dynamic changes in these systems are orchestrated by biochemical and mechanical microenvironments, which can be engineered and manipulated to probe their role in developmental and disease mechanisms. In particular, the in vitro investigation of mechanical cues has been the focus of recent research, where mechanical manipulations imparting local as well as large-scale mechanical stresses aim to mimic in vivo tissue deformations which occur through proliferation, folding, invagination, and elongation. However, current in vitro approaches largely impose homogeneous mechanical changes via a host matrix and lack the required positional and directional specificity to mimic the diversity of in vivo scenarios. Thus, while organoids exhibit limited aspects of in vivo morphogenetic events, how local forces are coordinated to enable large-scale changes in tissue architecture remains a difficult question to address using current techniques. Nanoparticles, through their efficient internalization by cells and dispersion through extracellular matrices, have the ability to provide local or global, as well as passive or active modulation of mechanical stresses on organoids and tissues. In this review, we explore how nanoparticles can be used to manipulate matrix and tissue mechanics, and highlight their potential as tools for fate regulation through mechanotransduction in multicellular model systems.

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<![CDATA[Comparative Transcriptome Analysis Reveals New lncRNAs Responding to Salt Stress in Sweet Sorghum]]> https://www.researchpad.co/product?articleinfo=Nda266021-f0b6-42f5-951c-1a0cb7ff7a4e

Long non-coding RNAs (lncRNAs) can enhance plant stress resistance by regulating the expression of functional genes. Sweet sorghum is a salt-tolerant energy crop. However, little is known about how lncRNAs in sweet sorghum respond to salt stress. In this study, we identified 126 and 133 differentially expressed lncRNAs in the salt-tolerant M-81E and the salt-sensitive Roma strains, respectively. Salt stress induced three new lncRNAs in M-81E and inhibited two new lncRNAs in Roma. These lncRNAs included lncRNA13472, lncRNA11310, lncRNA2846, lncRNA26929, and lncRNA14798, which potentially function as competitive endogenous RNAs (ceRNAs) that influence plant responses to salt stress by regulating the expression of target genes related to ion transport, protein modification, transcriptional regulation, and material synthesis and transport. Additionally, M-81E had a more complex ceRNA network than Roma. This study provides new information regarding lncRNAs and the complex regulatory network underlying salt-stress responses in sweet sorghum.

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<![CDATA[Dynamic Modeling of CHO Cell Metabolism Using the Hybrid Cybernetic Approach With a Novel Elementary Mode Analysis Strategy]]> https://www.researchpad.co/product?articleinfo=Nac8afc15-f00e-4d03-8f37-9b20004340ce

Chinese hamster ovary (CHO) cell culture has a major importance on the production of biopharmaceuticals, including recombinant therapeutic proteins such as monoclonal antibodies (MAb). Mathematical modeling of biological systems can successfully assess metabolism complexity while providing logical and systematic methods for relevant genetic target and culture parameter identification toward cell growth and productivity improvements. Most modeling approaches on CHO cells have been performed under stationary constraints, and only a few dynamic models have been presented on simplified reaction sets, due to substantial overparameterization problems. The hybrid cybernetic modeling (HCM) approach has been recently used to describe the dynamic behavior by incorporating regulation between different metabolic states by elementary mode participation control, with sets of equations evaluated by objective functions. However, as metabolic networks evaluated are constructed toward a genomic scale, and cell compartmentalization is considered, identification of the active set becomes more difficult as EM number exponentially grows. Thus, the development of robust approaches for EM active set selection and analysis with smaller computational requirements is required to impulse the use of cybernetic modeling on larger up to genome-scale networks. In this report, a novel elementary mode selection strategy, based on a polar representation of the convex solution space is presented and coupled to a cybernetic approach to model the dynamic physiologic and metabolic behavior of CHO-S cell cultures. The proposed Polar Space Yield Analysis (PSYA) was compared to other reported elementary mode selection approaches derived from Common Metabolic Objective Analysis (CMOA) used in Flux Balance Analysis (FBA), Yield Space Analysis (YSA), and Lumped Yield Space Analysis (LYSA). For this purpose, exponential growth phase dynamic metabolic models were calculated using kinetic rate equations based on previously modeled growth parameters. Finally, complete culture dynamic metabolic flux models were constructed using the HCM approach with selected elementary mode sets. The yield space elementary mode- and the polar space elementary mode- hybrid cybernetic models presented the best fits and performances. Also, a flux reaction perturbation prediction approach based on the polar yield solution space resulted useful for metabolic network flux distribution capability analysis and identification of potential genetic modifications targets.

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<![CDATA[Predicting Concussion Outcome by Integrating Finite Element Modeling and Network Analysis]]> https://www.researchpad.co/product?articleinfo=N73d9aa5f-5f1f-407c-9ac4-96b244119030

Concussion is a significant public health problem affecting 1.6–2.4 million Americans annually. An alternative to reducing the burden of concussion is to reduce its incidence with improved protective equipment and injury mitigation systems. Finite element (FE) models of the brain response to blunt trauma are often used to estimate injury potential and can lead to improved helmet designs. However, these models have yet to incorporate how the patterns of brain connectivity disruption after impact affects the relay of information in the injured brain. Furthermore, FE brain models typically do not consider the differences in individual brain structural connectivities and their purported role in concussion risk. Here, we use graph theory techniques to integrate brain deformations predicted from FE modeling with measurements of network efficiency to identify brain regions whose connectivity characteristics may influence concussion risk. We computed maximum principal strain in 129 brain regions using head kinematics measured from 53 professional football impact reconstructions that included concussive and non-concussive cases. In parallel, using diffusion spectrum imaging data from 30 healthy subjects, we simulated structural lesioning of each of the same 129 brain regions. We simulated lesioning by removing each region one at a time along with all its connections. In turn, we computed the resultant change in global efficiency to identify regions important for network communication. We found that brain regions that deformed the most during an impact did not overlap with regions most important for network communication (Pearson's correlation, ρ = 0.07; p = 0.45). Despite this dissimilarity, we found that predicting concussion incidence was equally accurate when considering either areas of high strain or of high importance to global efficiency. Interestingly, accuracy for concussion prediction varied considerably across the 30 healthy connectomes. These results suggest that individual network structure is an important confounding variable in concussion prediction and that further investigation of its role may improve concussion prediction and lead to the development of more effective protective equipment.

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<![CDATA[Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche]]> https://www.researchpad.co/product?articleinfo=N33218ec5-a5a1-497e-a794-d97a9758a778

The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. With the current acceptance rate of donor lungs of only 20%, rescuing even one half of the rejected donor lungs would increase the number of transplantable lungs threefold, to 60%. We review recent advances in lung bioengineering that have potential to repair the epithelial and vascular compartments of the lung. Our focus is on the long-term support and recovery of the lung ex vivo, and the replacement of defective epithelium with healthy therapeutic cells. To this end, we first review the roles of the lung epithelium and vasculature, with focus on the alveolar-capillary membrane, and then discuss the available and emerging technologies for ex vivo bioengineering of the lung by decellularization and recellularization. While there have been many meritorious advances in these technologies for recovering marginal quality lungs to the levels needed to meet the standards for transplantation – many challenges remain, motivating further studies of the extended ex vivo support and interventions in the lung. We propose that the repair of injured epithelium with preservation of quiescent vasculature will be critical for the immediate blood supply to the lung and the lung survival and function following transplantation.

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