scholarly journals Caged Dexamethasone/Quercetin Nanoparticles, Formed of the Morphogenetic Active Inorganic Polyphosphate, are Strong Inducers of MUC5AC

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 64 ◽  
Author(s):  
Meik Neufurth ◽  
Xiaohong Wang ◽  
Shunfeng Wang ◽  
Heinz C. Schröder ◽  
Werner E. G. Müller
Keyword(s):  
A549 Cells ◽  
Marine Species ◽  
Metabolic Energy ◽  
Inorganic Polyphosphate ◽  
Mucin Expression ◽  
Supporting Effect ◽  
Plant Metabolite ◽  
The Individual ◽  
Amorphous Nanoparticles ◽  
Secondary Plant Metabolite

Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the MUC5AC gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.

scholarly journals Morphogenetic (Mucin Expression) as Well as Potential Anti-Corona Viral Activity of the Marine Secondary Metabolite Polyphosphate on A549 Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 639
Author(s):  
Werner E. G. Müller ◽  
Meik Neufurth ◽  
Shunfeng Wang ◽  
Rongwei Tan ◽  
Heinz C. Schröder ◽  
...  
Keyword(s):  
Cell Attachment ◽  
Blood Platelets ◽  
A549 Cells ◽  
Bronchial Epithelium ◽  
Metabolic Energy ◽  
Marine Natural Product ◽  
Inorganic Polyphosphate ◽  
Mucin Expression

The mucus layer of the nasopharynx and bronchial epithelium has a barrier function against inhaled pathogens such as the coronavirus SARS-CoV-2. We recently found that inorganic polyphosphate (polyP), a physiological, metabolic energy (ATP)-providing polymer released from blood platelets, blocks the binding of the receptor binding domain (RBD) to the cellular ACE2 receptor in vitro. PolyP is a marine natural product and is abundantly present in marine bacteria. Now, we have approached the in vivo situation by studying the effect of polyP on the human alveolar basal epithelial A549 cells in a mucus-like mucin environment. These cells express mucins as well as the ectoenzymes alkaline phosphatase (ALP) and adenylate kinase (ADK), which are involved in the extracellular production of ATP from polyP. Mucin, integrated into a collagen-based hydrogel, stimulated cell growth and attachment. The addition of polyP to the hydrogel significantly increased cell attachment and also the expression of the membrane-tethered mucin MUC1 and the secreted mucin MUC5AC. The increased synthesis of MUC1 was also confirmed by immunostaining. This morphogenetic effect of polyP was associated with a rise in extracellular ATP level. We conclude that the nontoxic and non-immunogenic polymer polyP could possibly also exert a protective effect against SARS-CoV-2-cell attachment; first, by stimulating the innate antiviral response by strengthening the mucin barrier with its antimicrobial proteins, and second, by inhibiting virus attachment to the cells, as deduced from the reduction in the strength of binding between the viral RBD and the cellular ACE2 receptor.

scholarly journals The Potential Production of the Bioactive Compound Pinene Using Whey Permeate

Processes ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 263 ◽  
Author(s):  
Derrick Risner ◽  
Maria L. Marco ◽  
Sara A. Pace ◽  
Edward S. Spang
Keyword(s):  
Scale Up ◽  
Oxygen Demand ◽  
Bioactive Compound ◽  
Waste Streams ◽  
Significant Cost ◽  
Whey Permeate ◽  
Low Concentrations ◽  
Additional Processing ◽  
Plant Metabolite ◽  
Secondary Plant Metabolite

Pinene is a secondary plant metabolite that has functional properties as a flavor additive as well as potential cognitive health benefits. Although pinene is present in low concentrations in several plants, it is possible to engineer microorganisms to produce pinene. However, feedstock cost is currently limiting the industrial scale-up of microbial pinene production. One potential solution is to leverage waste streams such as whey permeate as an alternative to expensive feedstocks. Whey permeate is a sterile-filtered dairy effluent that contains 4.5% weight/weight lactose, and it must be processed or disposed of due its high biochemical oxygen demand, often at significant cost to the producer. Approximately 180 million m3 of whey is produced annually in the U.S., and only half of this quantity receives additional processing for the recovery of lactose. Given that organisms such as recombinant Escherichia coli grow on untreated whey permeate, there is an opportunity for dairy producers to microbially produce pinene and reduce the biological oxygen demand of whey permeate via microbial lactose consumption. The process would convert a waste stream into a valuable coproduct. This review examines the current approaches for microbial pinene production, and the suitability of whey permeate as a medium for microbial pinene production.

scholarly journals RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1476 ◽  
Author(s):  
Mirjam Schilling ◽  
Anne Bridgeman ◽  
Nicki Gray ◽  
Jonny Hertzog ◽  
Philip Hublitz ◽  
...  
Keyword(s):  
Cell Death ◽  
Zika Virus ◽  
Dominant Role ◽  
A549 Cells ◽  
Effective Control ◽  
Type I ◽  
Type I Ifn ◽  
Structural Protein ◽  
Induced Apoptosis ◽  
The Individual

The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain. We show that RIG-I is the main sensor for ZIKV in A549 cells. Surprisingly, we observed that loss of RIG-I and consecutive type I interferon (IFN) production led to virus-induced apoptosis. ZIKV non-structural protein NS5 was reported to interfere with type I IFN receptor signaling. Additionally, we show that ZIKV NS5 inhibits type I IFN induction. Overall, our study highlights the importance of RIG-I-dependent ZIKV sensing for the prevention of virus-induced cell death and shows that NS5 inhibits the production of type I IFN.

scholarly journals In VitroModels for Studying Secondary Plant Metabolite Digestion and Bioaccessibility

2014 ◽  
Vol 13 (4) ◽  
pp. 413-436 ◽  
Author(s):  
M. Alminger ◽  
A.-M. Aura ◽  
T. Bohn ◽  
C. Dufour ◽  
S.N. El ◽  
...  
Keyword(s):  
Plant Metabolite ◽  
Secondary Plant Metabolite ◽  
Secondary Plant

scholarly journals Combining structural and bioactivity-based fingerprints improves prediction performance and scaffold-hopping capability

2019 ◽  
Author(s):  
Oliver Laufkötter ◽  
Noé Sturm ◽  
Jürgen Bajorath ◽  
Ola Engkvist ◽  
Hongming Chen
Keyword(s):  
High Throughput Screening ◽  
Synergistic Effects ◽  
Predictive Performance ◽  
Small Subset ◽  
Scaffold Hopping ◽  
Activity Prediction ◽  
Importance Analysis ◽  
Supporting Effect ◽  
Overall Performance ◽  
The Individual

This study aims at improving upon existing activity predictions methods by augmenting chemical structure fingerprints with bio-activity based fingerprints derived from high-throughput screening (HTS) data (HTSFPs). The HTSFPs were generated from HTS data obtained from PubChem and combined with an ECFP4 structural fingerprint. The combined experimental and structural fingerprint (CESFP) was benchmarked against the individual ECFP4 and HTSFP fingerprints. Results showed that the CESFP has improved predictive performance as well as scaffold hopping capability. The CESFP identified unique compounds compared to both the ECFP4 and the HTSFP fingerprint indicating synergistic effects between the two fingerprints. A feature importance analysis showed that a small subset of the HTSFP features contribute most to the overall performance of the CESFP. This combined approach allows for activity prediction of compounds with only sparse HTSFPs due to the supporting effect from the structural fingerprint.

scholarly journals Combining structural and bioactivity-based fingerprints improves prediction performance and scaffold-hopping capability

2019 ◽  
Author(s):  
Oliver Laufkötter ◽  
Noé Sturm ◽  
Jürgen Bajorath ◽  
Ola Engkvist ◽  
Hongming Chen
Keyword(s):  
High Throughput Screening ◽  
Synergistic Effects ◽  
Predictive Performance ◽  
Small Subset ◽  
Scaffold Hopping ◽  
Activity Prediction ◽  
Importance Analysis ◽  
Supporting Effect ◽  
Overall Performance ◽  
The Individual

This study aims at improving upon existing activity predictions methods by augmenting chemical structure fingerprints with bio-activity based fingerprints derived from high-throughput screening (HTS) data (HTSFPs). The HTSFPs were generated from HTS data obtained from PubChem and combined with an ECFP4 structural fingerprint. The combined experimental and structural fingerprint (CESFP) was benchmarked against the individual ECFP4 and HTSFP fingerprints. Results showed that the CESFP has improved predictive performance as well as scaffold hopping capability. The CESFP identified unique compounds compared to both the ECFP4 and the HTSFP fingerprint indicating synergistic effects between the two fingerprints. A feature importance analysis showed that a small subset of the HTSFP features contribute most to the overall performance of the CESFP. This combined approach allows for activity prediction of compounds with only sparse HTSFPs due to the supporting effect from the structural fingerprint.

scholarly journals Impact of the secondary plant metabolite Cucurbitacin B on the demographical traits of the melon aphid, Aphis gossypii

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hafiz Kamran Yousaf ◽  
Tisheng Shan ◽  
Xuewei Chen ◽  
Kangsheng Ma ◽  
Xueyan Shi ◽  
...  
Keyword(s):  
Aphis Gossypii ◽  
Cucurbitacin B ◽  
Plant Metabolite ◽  
Melon Aphid ◽  
Secondary Plant Metabolite ◽  
Secondary Plant

Which Muscles Power the Human Running Stride?

2012 ◽  
Author(s):  
Tim W. Dorn ◽  
Yi-Chung Lin ◽  
Anthony G. Schache ◽  
Marcus G. Pandy
Keyword(s):  
Muscle Power ◽  
Center Of Mass ◽  
The Body ◽  
Metabolic Energy ◽  
Running Speed ◽  
Limb Coordination ◽  
External Power ◽  
Muscle Groups ◽  
The Individual ◽  
Human Running

Running is a physically demanding activity that requires explosive delivery of muscle power to the ground during stance, and precise, yet rapid limb coordination during swing. In particular, as running speed increases, greater metabolic energy in the form of muscle mechanical work is required to power the motion of: i) the center-of-mass (i.e., external power); and ii) the individual limb segments (i.e., internal power) [1,2]. The purpose of this study was to quantify the contributions that individual muscles make to the external and internal power of the body across a range of running speeds so as to identify the key muscle groups in coordinating a full running stride.

scholarly journals The response of the Golgi complex to microtubule alterations: the roles of metabolic energy and membrane traffic in Golgi complex organization.

1989 ◽  
Vol 109 (5) ◽  
pp. 2081-2088 ◽  
Author(s):  
J R Turner ◽  
A M Tartakoff
Keyword(s):  
Golgi Complex ◽  
Membrane Traffic ◽  
Metabolic Energy ◽  
Microtubule Assembly ◽  
Metabolic Inhibitors ◽  
Microtubule Depolymerization ◽  
Immunofluorescent Localization ◽  
Complex Organization ◽  
The Individual ◽  
Energy Dependent

A striking example of the interrelation between the Golgi complex (GC) and microtubules is the reversible fragmentation and dispersal of the GC which occurs upon microtubule depolymerization. We have characterized dispersal of the GC after nocodazole treatment as well as its recovery from the dispersed state by immunofluorescent localization of beta 1, 4-galactosyltransferase in Madin-Darby bovine kidney cells. Immunofluorescent anti-tubulin staining allowed simultaneous examination of the microtubule array. Based on our results, dispersal can be divided into a three-step process: microtubule depolymerization, GC fragmentation, and fragment dispersal. In cells treated with metabolic inhibitors after microtubule depolymerization, neither fragmentation nor dispersal occur, despite the absence of assembled microtubules. Thus, fragmentation is energy dependent and not tightly linked to microtubule depolymerization. The slowing of fragmentation and dispersal by monensin or ammonium chloride, as well as progressive inhibition at less than 34 degrees C, suggest that ongoing membrane traffic is required for these processes. Similarly, recovery may be separated into four steps: microtubule depolymerization, GC fragment centralization, fragment coalescence, and polarization of the reticular GC network. Fragment centralization and coalescence were arrested by metabolic inhibitors, despite the presence of microtubules. Neither monensin nor ammonium choride inhibited GC recovery. Partial inhibition of recovery at reduced temperatures paralleled the extent of microtubule assembly. These data demonstrate that dispersal and recovery are multi-step operations, and that the individual steps differ in temperature dependence, energy dependence, and sensitivity to ionic perturbation. GC distribution and microtubule status have also been clearly dissociate, thereby proving that organization of the GC is an active process that is not simply determined by microtubule binding. Furthermore, the results indicate that ongoing intra-GC membrane traffic may participate in fragmentation and dispersal.

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