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Biomolecules, Volume 11, Issue 11 (November 2021) – 193 articles

Cover Story (view full-size image): Experiments were carried out on glucosinolates (GSLs) from Brassicaceae plants as nutraceutical food for the control of Nosema ceranae, a fungal pathogen which threatened honeybee survival worldwide, in colonies of Apis mellifera. Honeybees were shown to be able to metabolize ingested GSLs from Brassica nigra and Eruca sativa defatted seed meal into the bioactive compounds isothiocyanates by a myrosinase-like enzyme in gut tissues. GSL enriched patties showed a good tolerability, and E. sativa in particular appeared to significantly decrease the number of N. ceranae copies in naturally infected honeybees. The results are indicative of a specific effect on N. ceranae infection in managed Apis mellifera colonies depending on the GSL activation within the target organ. View this paper
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Article
β-Dystroglycan Restoration and Pathology Progression in the Dystrophic mdx Mouse: Outcome and Implication of a Clinically Oriented Study with a Novel Oral Dasatinib Formulation
Biomolecules 2021, 11(11), 1742; https://doi.org/10.3390/biom11111742 - 22 Nov 2021
Cited by 1 | Viewed by 793
Abstract
ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mdx mice, a 4-week subcutaneous treatment with dasatinib (DAS), a [...] Read more.
ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mdx mice, a 4-week subcutaneous treatment with dasatinib (DAS), a pan-Src-TKs inhibitor approved as anti-leukemic agent, increased muscle β-DG, with minimal amelioration of morphofunctional indices. To address possible dose/pharmacokinetic (PK) issues, a new oral DAS/hydroxypropyl(HP)-β-cyclodextrin(CD) complex was developed and chronically administered to mdx mice. The aim was to better assess the role of β-DG in pathology progression, meanwhile confirming DAS mechanism of action over the long-term, along with its efficacy and tolerability. The 4-week old mdx mice underwent a 12-week treatment with DAS/HP-β-CD10% dissolved in drinking water, at 10 or 20 mg/kg/day. The outcome was evaluated via in vivo/ex vivo disease-relevant readouts. Oral DAS/HP-β-CD efficiently distributed in mdx mice plasma and tissues in a dose-related fashion. The new DAS formulation confirmed its main upstream mechanism of action, by reducing β-DG phosphorylation and restoring its levels dose-dependently in both diaphragm and gastrocnemius muscle. However, it modestly improved in vivo neuromuscular function, ex vivo muscle force, and histopathology, although the partial recovery of muscle elasticity and the decrease of CK and LDH plasma levels suggest an increased sarcolemmal stability of dystrophic muscles. Our clinically oriented study supports the interest in this new, pediatric-suitable DAS formulation for proper exposure and safety and for enhancing β-DG expression. This latter mechanism is, however, not sufficient by itself to impact on pathology progression. In-depth analyses will be dedicated to elucidating the mechanism limiting DAS effectiveness in dystrophic settings, meanwhile assessing its potential synergy with dystrophin-based molecular therapies. Full article
(This article belongs to the Special Issue Molecular Basis of Neuromuscular Diseases)
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Article
Emergence and Enhancement of Ultrasensitivity through Posttranslational Modulation of Protein Stability
Biomolecules 2021, 11(11), 1741; https://doi.org/10.3390/biom11111741 - 22 Nov 2021
Cited by 1 | Viewed by 494
Abstract
Signal amplification in biomolecular networks converts a linear input to a steeply sigmoid output and is central to a number of cellular functions including proliferation, differentiation, homeostasis, adaptation, and biological rhythms. One canonical signal amplifying motif is zero-order ultrasensitivity that is mediated through [...] Read more.
Signal amplification in biomolecular networks converts a linear input to a steeply sigmoid output and is central to a number of cellular functions including proliferation, differentiation, homeostasis, adaptation, and biological rhythms. One canonical signal amplifying motif is zero-order ultrasensitivity that is mediated through the posttranslational modification (PTM) cycle of signaling proteins. The functionality of this signaling motif has been examined conventionally by supposing that the total amount of the protein substrates remains constant, as by the classical Koshland–Goldbeter model. However, covalent modification of signaling proteins often results in changes in their stability, which affects the abundance of the protein substrates. Here, we use mathematical models to explore the signal amplification properties in such scenarios and report some novel aspects. Our analyses indicate that PTM-induced protein stabilization brings the enzymes closer to saturation. As a result, ultrasensitivity may emerge or is greatly enhanced, with a steeper sigmoidal response, higher magnitude, and generally longer response time. In cases where PTM destabilizes the protein, ultrasensitivity can be regained through changes in the activities of the involved enzymes or from increased protein synthesis. Importantly, ultrasensitivity is not limited to modified or unmodified protein substrates—when protein turnover is considered, the total free protein substrate can also exhibit ultrasensitivity under several conditions. When full enzymatic reactions are used instead of Michaelis–Menten kinetics for the modeling, the total free protein substrate can even exhibit nonmonotonic dose–response patterns. It is conceivable that cells use inducible protein stabilization as a strategy in the signaling network to boost signal amplification while saving energy by keeping the protein substrate levels low at basal conditions. Full article
(This article belongs to the Special Issue Computational Approaches for the Study of Biomolecular Networks)
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Article
Quantitative Morphological Analysis of Filamentous Microorganisms in Cocultures and Monocultures: Aspergillus terreus and Streptomyces rimosus Warfare in Bioreactors
Biomolecules 2021, 11(11), 1740; https://doi.org/10.3390/biom11111740 - 22 Nov 2021
Viewed by 540
Abstract
The aim of this study was to quantitatively characterize the morphology of the filamentous microorganisms Aspergillus terreus ATCC 20542 and Streptomyces rimosus ATCC 10970, cocultivated in stirred tank bioreactors, and to characterize their mutual influence with the use of quantitative image analysis. Three [...] Read more.
The aim of this study was to quantitatively characterize the morphology of the filamentous microorganisms Aspergillus terreus ATCC 20542 and Streptomyces rimosus ATCC 10970, cocultivated in stirred tank bioreactors, and to characterize their mutual influence with the use of quantitative image analysis. Three distinct coculture initiation strategies were applied: preculture versus preculture, spores versus spores and preculture versus preculture with time delay for one of the species. Bioreactor cocultures were accompanied by parallel monoculture controls. The results recorded for the mono- and cocultures were compared in order to investigate the effect of cocultivation on the morphological evolution of A. terreus and S. rimosus. Morphology-related observations were also confronted with the analysis of secondary metabolism. The morphology of the two studied filamentous species strictly depended on the applied coculture initiation strategy. In the cocultures initiated by the simultaneous inoculation, S. rimosus gained domination or advance over A. terreus. The latter microorganism dominated only in these experiments in which S. rimosus was introduced with a delay. Full article
(This article belongs to the Collection Feature Papers in Synthetic Biology and Bioengineering)
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Review
The Role of Matrix Metalloproteinases in Endometriosis: A Potential Target
Biomolecules 2021, 11(11), 1739; https://doi.org/10.3390/biom11111739 - 22 Nov 2021
Viewed by 838
Abstract
Endometriosis is a condition that is influenced by hormones and involves stroma and glands being found outside the uterus; there are increases in proliferation, invasion, internal bleeding, and fibrosis. Matrix metalloproteinases (MMPs) have been suggested to be crucial in the progression of invasion. [...] Read more.
Endometriosis is a condition that is influenced by hormones and involves stroma and glands being found outside the uterus; there are increases in proliferation, invasion, internal bleeding, and fibrosis. Matrix metalloproteinases (MMPs) have been suggested to be crucial in the progression of invasion. The MMP family includes calcium-dependent zinc-containing endopeptidases, some of which not only affect the process of cell invasion but also participate in other physiological and pathological processes, such as angiogenesis and fibrosis. MMPs act as downstream-targeted molecules and their expression can be regulated by numerous factors such as estrogen, oxidative stress, cytokines, and environmental contaminants. Given their unique roles in endometriosis, MMPs may become effective biomarkers of endometriosis in the future. In the present review, we summarize the current literature on MMPs regarding their classification, function, and potential value for endometriosis, which may contribute to our knowledge of MMPs and MMP-targeted interventions. Full article
(This article belongs to the Section Molecular Reproduction)
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Review
Eclipta prostrata (L.) L. (Asteraceae): Ethnomedicinal Uses, Chemical Constituents, and Biological Activities
Biomolecules 2021, 11(11), 1738; https://doi.org/10.3390/biom11111738 - 22 Nov 2021
Cited by 2 | Viewed by 1176
Abstract
Eclipta prostrata (L.) L. (Syn.: Eclipta alba (L.) Hassak, Family: Asteraceae) is an important medicinal plant in the tropical and subtropical regions. It is widely used in treating various diseases of skin, liver and stomach in India, Nepal, Bangladesh, and other countries. The [...] Read more.
Eclipta prostrata (L.) L. (Syn.: Eclipta alba (L.) Hassak, Family: Asteraceae) is an important medicinal plant in the tropical and subtropical regions. It is widely used in treating various diseases of skin, liver and stomach in India, Nepal, Bangladesh, and other countries. The main aim of this review was to collect and analyze the available information on traditional uses, phytoconstituents, and biological activities of E. prostrata. The scientific information was collected from the online bibliographic databases such as Scopus, MEDLINE/PubMed, Google Scholar, SciFinder, etc. and books and proceedings. The active phytochemicals were coumestan derivatives, phenolic acid derivatives, flavonoids, triterpenoid and steroid saponins, substituted thiophenes, etc. Various extracts and isolated compounds of E. prostrata showed a wide range of biological activities such as antimicrobial, anticancer, hepatoprotective, neuroprotective and hair growth promoting activities. Relatively a few studies have been performed to reveal the exact phytoconstituents responsible for their corresponding pharmacological activities. Future studies should focus on detailed mechanism based studies using animal models and clinical studies. Full article
(This article belongs to the Topic Compounds with Medicinal Value)
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Article
Heterologous Expression and Assembly of Human TLR Signaling Components in Saccharomyces cerevisiae
Biomolecules 2021, 11(11), 1737; https://doi.org/10.3390/biom11111737 - 22 Nov 2021
Viewed by 1223
Abstract
Toll-like receptor (TLR) signaling is key to detect pathogens and initiating inflammation. Ligand recognition triggers the assembly of supramolecular organizing centers (SMOCs) consisting of large complexes composed of multiple subunits. Building such signaling hubs relies on Toll Interleukin-1 Receptor (TIR) and Death Domain [...] Read more.
Toll-like receptor (TLR) signaling is key to detect pathogens and initiating inflammation. Ligand recognition triggers the assembly of supramolecular organizing centers (SMOCs) consisting of large complexes composed of multiple subunits. Building such signaling hubs relies on Toll Interleukin-1 Receptor (TIR) and Death Domain (DD) protein-protein interaction domains. We have expressed TIR domain-containing components of the human myddosome (TIRAP and MyD88) and triffosome (TRAM and TRIF) SMOCs in Saccharomyces cerevisiae, as a platform for their study. Interactions between the TLR4 TIR domain, TIRAP, and MyD88 were recapitulated in yeast. Human TIRAP decorated the yeast plasma membrane (PM), except for the bud neck, whereas MyD88 was found at cytoplasmic spots, which were consistent with endoplasmic reticulum (ER)-mitochondria junctions, as evidenced by co-localization with Mmm1 and Mdm34, components of the ER and Mitochondria Encounter Structures (ERMES). The formation of MyD88-TIRAP foci at the yeast PM was reinforced by co-expression of a membrane-bound TLR4 TIR domain. Mutations in essential residues of their TIR domains aborted MyD88 recruitment by TIRAP, but their respective subcellular localizations were unaltered. TRAM and TRIF, however, did not co-localize in yeast. TRAM assembled long PM-bound filaments that were disrupted by co-expression of the TLR4 TIR domain. Our results evidence that the yeast model can be exploited to study the interactions and subcellular localization of human SMOC components in vivo. Full article
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Article
Pyrazines Biosynthesis by Bacillus Strains Isolated from Natto Fermented Soybean
Biomolecules 2021, 11(11), 1736; https://doi.org/10.3390/biom11111736 - 22 Nov 2021
Cited by 1 | Viewed by 650
Abstract
Pyrazines are organic compounds with a varied, intense aroma of roasted nuts, occasionally with hints of baked potatoes, almonds, and others. As a result, they are used in the food industry as food flavorings. Biosynthesis of pyrazines using microorganisms in environmentally friendly conditions [...] Read more.
Pyrazines are organic compounds with a varied, intense aroma of roasted nuts, occasionally with hints of baked potatoes, almonds, and others. As a result, they are used in the food industry as food flavorings. Biosynthesis of pyrazines using microorganisms in environmentally friendly conditions is an alternative to chemical synthesis. However, screening is required to isolate efficient producer strains for efficient biosynthesis of this compound. The study’s goal was to assess the ability of Bacillus subtilis cultures isolated from natto (fermented soybeans) to biosynthesize a broad range of alkylpyrazines. B. subtilis isolated cultures were found to be capable of producing 2-methylpyrazine, 2,3-dimethylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, 2,3,5-trimethylpyrazine, and 2,3,5,6-tetramethylpyrazine. As a result of the screening, two cultures of B. subtilis capable of producing alkylpyrazines were isolated. At a total concentration of 3261 µg/L, the BcP4 strain primarily produced 2-methylpyrazine (690 µg/L), 2,3-dimethylpyrazine (680 µg/L), and 2,6-dimethylpyrazine (1891 µg/L). At a total concentration of 558 mg/L, the BcP21 strain produced 2,5-dimethylpyrazine (4.5 mg/L), 2,3,5-trimethylpyrazine (52.6 mg/L), and 2,3,5,6-tetramethylpyrazine (501.1 mg/L). The results show that different B. subtilis strains are predisposed to produce different alkylpyrazines. Full article
(This article belongs to the Collection Feature Papers in Synthetic Biology and Bioengineering)
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Article
Novel Bi-Modular GH19 Chitinase with Broad pH Stability from a Fibrolytic Intestinal Symbiont of Eisenia fetida, Cellulosimicrobium funkei HY-13
Biomolecules 2021, 11(11), 1735; https://doi.org/10.3390/biom11111735 - 21 Nov 2021
Viewed by 616
Abstract
Endo-type chitinase is the principal enzyme involved in the breakdown of N-acetyl-d-glucosamine-based oligomeric and polymeric materials through hydrolysis. The gene (966-bp) encoding a novel endo-type chitinase (ChiJ), which is comprised of an N-terminal chitin-binding domain type 3 and a C-terminal [...] Read more.
Endo-type chitinase is the principal enzyme involved in the breakdown of N-acetyl-d-glucosamine-based oligomeric and polymeric materials through hydrolysis. The gene (966-bp) encoding a novel endo-type chitinase (ChiJ), which is comprised of an N-terminal chitin-binding domain type 3 and a C-terminal catalytic glycoside hydrolase family 19 domain, was identified from a fibrolytic intestinal symbiont of the earthworm Eisenia fetida, Cellulosimicrobium funkei HY-13. The highest endochitinase activity of the recombinant enzyme (rChiJ: 30.0 kDa) toward colloidal shrimp shell chitin was found at pH 5.5 and 55 °C and was considerably stable in a wide pH range (3.5–11.0). The enzyme exhibited the highest biocatalytic activity (338.8 U/mg) toward ethylene glycol chitin, preferentially degrading chitin polymers in the following order: ethylene glycol chitin > colloidal shrimp shell chitin > colloidal crab shell chitin. The enzymatic hydrolysis of N-acetyl-β-d-chitooligosaccharides with a degree of polymerization from two to six and colloidal shrimp shell chitin yielded primarily N,N-diacetyl-β-d-chitobiose together with a small amount of N-acetyl-d-glucosamine. The high chitin-degrading ability of inverting rChiJ with broad pH stability suggests that it can be exploited as a suitable biocatalyst for the preparation of N,N-diacetyl-β-d-chitobiose, which has been shown to alleviate metabolic dysfunction associated with type 2 diabetes. Full article
(This article belongs to the Collection Feature Papers in Enzymology)
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Article
Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment
Biomolecules 2021, 11(11), 1734; https://doi.org/10.3390/biom11111734 - 21 Nov 2021
Cited by 2 | Viewed by 495
Abstract
Leptin modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflammatory cytokine levels [...] Read more.
Leptin modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflammatory cytokine levels in inguinal fat and liver of chronic central leptin infused (L), pair-fed (PF), and control rats. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was increased in inguinal fat and reduced in liver of L rats. Phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NFkB) was increased in inguinal fat of L rats, together with a pro-inflammatory cytokine profile, while in the liver activation of JNK and NFkB were reduced and an anti-inflammatory pattern was found. Phosphorylation of the insulin receptor, Akt and mechanistic target of rapamycin was decreased in inguinal fat and increased in liver of L rats. There was a direct relationship between pSTAT3 and JNK and a negative correlation of Akt with pSTAT3 and JNK in both tissues. These results indicate that the effects of chronically increased leptin on insulin-related signaling are tissue-specific and suggest that inflammation plays a relevant role in the crosstalk between leptin and insulin signaling. Full article
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Article
Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
Biomolecules 2021, 11(11), 1733; https://doi.org/10.3390/biom11111733 - 20 Nov 2021
Viewed by 1162
Abstract
Single nucleotide polymorphisms (SNPs) help to understand the phenotypic variations in humans. Genome-wide association studies (GWAS) have identified SNPs located in the tumor protein 63 (TP63) locus to be associated with the genetic susceptibility of cancers. However, there is a lack of in-depth [...] Read more.
Single nucleotide polymorphisms (SNPs) help to understand the phenotypic variations in humans. Genome-wide association studies (GWAS) have identified SNPs located in the tumor protein 63 (TP63) locus to be associated with the genetic susceptibility of cancers. However, there is a lack of in-depth characterization of the structural and functional impacts of the SNPs located at the TP63 gene. The current study was designed for the comprehensive characterization of the coding and non-coding SNPs in the human TP63 gene for their functional and structural significance. The functional and structural effects of the SNPs were investigated using a wide variety of computational tools and approaches, including molecular dynamics (MD) simulation. The deleterious impact of eight nonsynonymous SNPs (nsSNPs) affecting protein stability, structure, and functions was measured by using 13 bioinformatics tools. These eight nsSNPs are in highly conserved positions in protein and were predicted to decrease protein stability and have a deleterious impact on the TP63 protein function. Molecular docking analysis showed five nsSNPs to reduce the binding affinity of TP63 protein to DNA with significant results for three SNPs (R319H, G349E, and C347F). Further, MD simulations revealed the possible disruption of TP63 and DNA binding, hampering the essential protein function. PolymiRTS study found five non-coding SNPs in miRNA binding sites, and the GTEx portal recognized five eQTLs SNPs in single tissue of the lung, heart (LV), and cerebral hemisphere (brain). Characterized nsSNPs and non-coding SNPs will help researchers to focus on TP63 gene loci and ascertain their association with certain diseases. Full article
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Article
Assaying Paenibacillus alvei CsaB-Catalysed Ketalpyruvyltransfer to Saccharides by Measurement of Phosphate Release
Biomolecules 2021, 11(11), 1732; https://doi.org/10.3390/biom11111732 - 20 Nov 2021
Viewed by 583
Abstract
Ketalpyruvyltransferases belong to a widespread but little investigated class of enzymes, which utilise phosphoenolpyruvate (PEP) for the pyruvylation of saccharides. Pyruvylated saccharides play pivotal biological roles, ranging from protein binding to virulence. Limiting factors for the characterisation of ketalpyruvyltransferases are the availability of [...] Read more.
Ketalpyruvyltransferases belong to a widespread but little investigated class of enzymes, which utilise phosphoenolpyruvate (PEP) for the pyruvylation of saccharides. Pyruvylated saccharides play pivotal biological roles, ranging from protein binding to virulence. Limiting factors for the characterisation of ketalpyruvyltransferases are the availability of cognate acceptor substrates and a straightforward enzyme assay. We report on a fast ketalpyruvyltransferase assay based on the colorimetric detection of phosphate released during pyruvyltransfer from PEP onto the acceptor via complexation with Malachite Green and molybdate. To optimise the assay for the model 4,6-ketalpyruvyl::ManNAc-transferase CsaB from Paenibacillus alvei, a β-d-ManNAc-α-d-GlcNAc-diphosphoryl-11-phenoxyundecyl acceptor mimicking an intermediate of the bacterium’s cell wall glycopolymer biosynthesis pathway, upon which CsaB is naturally active, was produced chemo-enzymatically and used together with recombinant CsaB. Optimal assay conditions were 5 min reaction time at 37 °C and pH 7.5, followed by colour development for 1 h at 37 °C and measurement of absorbance at 620 nm. The structure of the generated pyruvylated product was confirmed by NMR spectroscopy. Using the established assay, the first kinetic constants of a 4,6-ketalpyuvyl::ManNAc-transferase could be determined; upon variation of the acceptor and PEP concentrations, a KM, PEP of 19.50 ± 3.50 µM and kcat, PEP of 0.21 ± 0.01 s−1 as well as a KM, Acceptor of 258 ± 38 µM and a kcat, Acceptor of 0.15 ± 0.01 s−1 were revealed. P. alvei CsaB was inactive on synthetic pNP-β-d-ManNAc and β-d-ManNAc-β-d-GlcNAc-1-OMe, supporting the necessity of a complex acceptor substrate. Full article
(This article belongs to the Special Issue Glycosylation—The Most Diverse Post-Translational Modification)
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Review
Piezoelectric Signals in Vascularized Bone Regeneration
Biomolecules 2021, 11(11), 1731; https://doi.org/10.3390/biom11111731 - 20 Nov 2021
Cited by 1 | Viewed by 1144
Abstract
The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating [...] Read more.
The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery. Full article
(This article belongs to the Special Issue New Insights into Stem Cell Regulation)
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Review
Do Neurotrophins Connect Neurological Disorders and Heart Diseases?
Biomolecules 2021, 11(11), 1730; https://doi.org/10.3390/biom11111730 - 19 Nov 2021
Cited by 1 | Viewed by 638
Abstract
Neurotrophins (NTs) are one of the most characterized neurotrophic factor family members and consist of four members in mammals. Growing evidence suggests that there is a complex inter- and bi-directional relationship between central nervous system (CNS) disorders and cardiac dysfunction, so-called “brain–heart axis”. [...] Read more.
Neurotrophins (NTs) are one of the most characterized neurotrophic factor family members and consist of four members in mammals. Growing evidence suggests that there is a complex inter- and bi-directional relationship between central nervous system (CNS) disorders and cardiac dysfunction, so-called “brain–heart axis”. Recent studies suggest that CNS disorders, including neurodegenerative diseases, stroke, and depression, affect cardiovascular function via various mechanisms, such as hypothalamic–pituitary–adrenal axis augmentation. Although this brain–heart axis has been well studied in humans and mice, the involvement of NT signaling in the axis has not been fully investigated. In the first half of this review, we emphasize the importance of NTs not only in the nervous system, but also in the cardiovascular system from the embryonic stage to the adult state. In the second half, we discuss the involvement of NTs in the pathogenesis of cardiovascular diseases, and then examine whether an alteration in NTs could serve as the mediator between neurological disorders and heart dysfunction. The further investigation we propose herein could contribute to finding direct evidence for the involvement of NTs in the axis and new treatment for cardiovascular diseases. Full article
(This article belongs to the Special Issue Metabolic and Neurotrophic Pathways Driving the Brain-Heart-Axis)
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Editorial
Nanoparticles as Vectors to Tackle Cancer
Biomolecules 2021, 11(11), 1729; https://doi.org/10.3390/biom11111729 - 19 Nov 2021
Viewed by 586
Abstract
The aim of this Special Issue, “Nanoparticles for cancer therapy”, was to offer readers a comprehensive and up-to-date insight into the various applications of nanoparticles in cancer treatments [...] Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Therapy)
Article
Pseudomonas fluorescens Showing Antifungal Activity against Macrophomina phaseolina, a Severe Pathogenic Fungus of Soybean, Produces Phenazine as the Main Active Metabolite
Biomolecules 2021, 11(11), 1728; https://doi.org/10.3390/biom11111728 - 19 Nov 2021
Cited by 2 | Viewed by 705
Abstract
Pseudomonas fluorescens 9 and Bacillus subtilis 54, proposed as biofungicides to control Macrophomina phaseolina, a dangerous pathogen of soybean and other crops, were grown in vitro to evaluate their ability to produce metabolites with antifungal activity. The aim of the manuscript was [...] Read more.
Pseudomonas fluorescens 9 and Bacillus subtilis 54, proposed as biofungicides to control Macrophomina phaseolina, a dangerous pathogen of soybean and other crops, were grown in vitro to evaluate their ability to produce metabolites with antifungal activity. The aim of the manuscript was to identify the natural compounds responsible for their antifungal activity. Only the culture filtrates of P. fluorescens 9 showed strong antifungal activity against M. phaseolina. Its organic extract contained phenazine and mesaconic acid (1 and 2), whose antifungal activity was tested against M. phaseolina, as well as Cercospora nicotianae and Colletotrichum truncatum, other pathogens of soybean; however, only compound 1 exhibited activity. The antifungal activity of compound 1 was compared to phenazine-1-carboxylic acid (PCA, 3), 2-hydroxyphenazine (2-OH P, 4), and various semisynthetic phenazine nitro derivatives in order to perform a structure–activity relationship (SAR) study. PCA and phenazine exhibited the same percentage of growth inhibition in M. phaseolina and C. truncatum, whereas PCA (3) showed lower activity against C. nicotianae than phenazine. 2-Hydroxyphenazine (4) showed no antifungal activity against M. phaseolina. The results of the SAR study showed that electron attractor (COOH and NO2) or repulsor (OH) groups significantly affect the antifungal growth, as well as their α- or β-location on the phenazine ring. Both PCA and phenazine could be proposed as biopesticides to control the soybean pathogens M. phaseolina, C. nicotianae, and C. truncatum, and these results should prompt an investigation of their large-scale production and their suitable formulation for greenhouse and field applications. Full article
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Article
Rhamnolipids as a Tool for Eradication of Trichosporon cutaneum Biofilm
Biomolecules 2021, 11(11), 1727; https://doi.org/10.3390/biom11111727 - 19 Nov 2021
Cited by 1 | Viewed by 495
Abstract
Microbial biofilms formed by pathogenic and antibiotic-resistant microorganisms represent a serious threat for public health in medicine and many industrial branches. Biofilms are involved in many persistent and chronic infections, the biofouling of water and food contamination. Therefore, current research is involved in [...] Read more.
Microbial biofilms formed by pathogenic and antibiotic-resistant microorganisms represent a serious threat for public health in medicine and many industrial branches. Biofilms are involved in many persistent and chronic infections, the biofouling of water and food contamination. Therefore, current research is involved in the development of new treatment strategies. Biofilm is a complex system, and thus all aspects of the measurement and monitoring of its growth and eradication in various conditions, including static and dynamic flow, are issues of great importance. The antibiofilm character of rhamnolipid mixtures produced by four Pseudomonas aeruginosa strains was studied under different conditions. For this purpose, the biofilm of opportunistic pathogen Trichosporon cutaneum was used and treated under static conditions (microscope glass coverslip in a Petri dish) and under dynamic conditions (a single-channel flow cell). The results show that the biological activity of rhamnolipids depends both on their properties and on the conditions of the biofilm formation. Therefore, this aspect must be taken into account when planning the experimental or application design. Full article
(This article belongs to the Collection Feature Papers in Biomacromolecules: Lipids)
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Article
Dynamic DNA Methylation Changes in the COMT Gene Promoter Region in Response to Mental Stress and Its Modulation by Transcranial Direct Current Stimulation
Biomolecules 2021, 11(11), 1726; https://doi.org/10.3390/biom11111726 - 19 Nov 2021
Cited by 1 | Viewed by 528
Abstract
Changes in epigenetic modifications present a mechanism how environmental factors, such as the experience of stress, can alter gene regulation. While stress-related disorders have consistently been associated with differential DNA methylation, little is known about the time scale in which these alterations emerge. [...] Read more.
Changes in epigenetic modifications present a mechanism how environmental factors, such as the experience of stress, can alter gene regulation. While stress-related disorders have consistently been associated with differential DNA methylation, little is known about the time scale in which these alterations emerge. We investigated dynamic DNA methylation changes in whole blood of 42 healthy male individuals in response to a stressful cognitive task, its association with concentration changes in cortisol, and its modulation by transcranial direct current stimulation (tDCS). We observed a continuous increase in COMT promotor DNA methylation which correlated with higher saliva cortisol levels and was still detectable one week later. However, this lasting effect was suppressed by concurrent activity-enhancing anodal tDCS to the dorsolateral prefrontal cortex. Our findings support the significance of gene-specific DNA methylation in whole blood as potential biomarkers for stress-related effects. Moreover, they suggest alternative molecular mechanisms possibly involved in lasting behavioral effects of tDCS. Full article
(This article belongs to the Special Issue Key Advances in Brain Stimulation)
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Article
Role of Inflammation and Redox Status on Doxorubicin-Induced Cardiotoxicity in Infant and Adult CD-1 Male Mice
Biomolecules 2021, 11(11), 1725; https://doi.org/10.3390/biom11111725 - 19 Nov 2021
Viewed by 773
Abstract
Doxorubicin (DOX) is a topoisomerase II inhibitor commonly used in the treatment of several types of cancer. Despite its efficacy, DOX can potentially cause fatal adverse effects, like cardiotoxicity. This work aimed to assess the role of inflammation in DOX-treated infant and adult [...] Read more.
Doxorubicin (DOX) is a topoisomerase II inhibitor commonly used in the treatment of several types of cancer. Despite its efficacy, DOX can potentially cause fatal adverse effects, like cardiotoxicity. This work aimed to assess the role of inflammation in DOX-treated infant and adult mice and its possible link to underlying cardiotoxicity. Two groups of CD-1 male mice of different ages (infants or adults) were subjected to biweekly DOX administrations, to reach a cumulative dose of 18.0 mg/kg, which corresponds approximately in humans to 100.6 mg/m2 for infants and 108.9 mg/m2 for adults a clinically relevant dose in humans. The classic plasmatic markers of cardiotoxicity increased, and that damage was confirmed by histopathological findings in both groups, although it was higher in adults. Moreover, in DOX-treated adults, an increase of cardiac fibrosis was observed, which was accompanied by an increase in specific inflammatory parameters, namely, macrophage M1 and nuclear factor kappa B (NF-κB) p65 subunit, with a trend toward increased levels of the tumor necrosis factor receptor 2 (TNFR2). On the other hand, the levels of myeloperoxidase (MPO) and interleukin (IL)-6 significantly decreased in DOX-treated adult animals. In infants, a significant increase in cardiac protein carbonylation and in the levels of nuclear factor erythroid-2 related factor 2 (Nrf2) was observed. In both groups, no differences were found in the levels of tumor necrosis factor (TNF-α), IL-1β, p38 mitogen-activated protein kinase (p38 MAPK) or NF-κB p52 subunit. In conclusion, using a clinically relevant dose of DOX, our study demonstrated that cardiac effects are associated not only with the intensity of the inflammatory response but also with redox response. Adult mice seemed to be more prone to DOX-induced cardiotoxicity by mechanisms related to inflammation, while infant mice seem to be protected from the damage caused by DOX, possibly by activating such antioxidant defenses as Nrf2. Full article
(This article belongs to the Special Issue Pharmacology of Cardiovascular Disease)
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Article
Interaction of the Escherichia coli HU Protein with Various Topological Forms of DNA
Biomolecules 2021, 11(11), 1724; https://doi.org/10.3390/biom11111724 - 19 Nov 2021
Cited by 2 | Viewed by 596
Abstract
E. coli histone-like protein HU has been shown to interact with different topological forms of DNA. Using radiolabeled HU, we examine the effects of DNA supercoiling on HU–DNA interactions. We show that HU binds preferentially to negatively supercoiled DNA and that the affinity [...] Read more.
E. coli histone-like protein HU has been shown to interact with different topological forms of DNA. Using radiolabeled HU, we examine the effects of DNA supercoiling on HU–DNA interactions. We show that HU binds preferentially to negatively supercoiled DNA and that the affinity of HU for DNA increases with increases in the negative superhelical density of DNA. Binding of HU to DNA is most sensitively influenced by DNA supercoiling within a narrow but physiologically relevant range of superhelicity (σ = −0.06–0). Under stoichiometric binding conditions, the affinity of HU for negatively supercoiled DNA (σ = −0.06) is more than 10 times higher than that for relaxed DNA at physiologically relevant HU/DNA mass ratios (e.g., 1:10). This binding preference, however, becomes negligible at HU/DNA mass ratios higher than 1:2. At saturation, HU binds both negatively supercoiled and relaxed DNA with similar stoichiometries, i.e., 5–6 base pairs per HU dimer. In our chemical crosslinking studies, we demonstrate that HU molecules bound to negatively supercoiled DNA are more readily crosslinked than those bound to linear DNA. At in vivo HU/DNA ratios, HU appears to exist predominantly in a tetrameric form on negatively supercoiled DNA and in a dimeric form on linear DNA. Using a DNA ligase-mediated nick closure assay, we show that approximately 20 HU dimers are required to constrain one negative supercoil on relaxed DNA. Although fewer HU dimers may be needed to constrain one negative supercoil on negatively supercoiled DNA, our results and estimates of the cellular level of HU argue against a major role for HU in constraining supercoils in vivo. We discuss our data within the context of the dynamic distribution of the HU protein in cells, where temporal and local changes of DNA supercoiling are known to take place. Full article
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Article
The Effect of Mycotoxins and Silymarin on Liver Lipidome of Mice with Non-Alcoholic Fatty Liver Disease
Biomolecules 2021, 11(11), 1723; https://doi.org/10.3390/biom11111723 - 19 Nov 2021
Cited by 2 | Viewed by 730
Abstract
Milk thistle-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum) is often used for the treatment of liver diseases because of the presence of its active component, silymarin. However, the co-occurrence of toxic mycotoxins in these [...] Read more.
Milk thistle-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum) is often used for the treatment of liver diseases because of the presence of its active component, silymarin. However, the co-occurrence of toxic mycotoxins in these preparations is quite frequent as well. The objective of this study was to investigate the changes in composition of liver lipidome and other clinical characteristics of experimental mice fed by a high-fat methionine-choline deficient diet inducing non-alcoholic fatty liver disease. The mice were exposed to (i) silymarin, (ii) mycotoxins (trichothecenes, enniatins, beauvericin, and altertoxins) and (iii) both silymarin and mycotoxins, and results were compared to the controls. The liver tissue extracts were analyzed by ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry. Using tools of univariate and multivariate statistical analysis, we were able to identify 48 lipid species from the classes of diacylglycerols, triacylglycerols, free fatty acids, fatty acid esters of hydroxy fatty acids and phospholipids clearly reflecting the dysregulation of lipid metabolism upon exposure to mycotoxin and/or silymarin. Full article
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Review
Novel Methylation Biomarkers for Colorectal Cancer Prognosis
Biomolecules 2021, 11(11), 1722; https://doi.org/10.3390/biom11111722 - 19 Nov 2021
Cited by 1 | Viewed by 933
Abstract
Colorectal cancer (CRC) comprises the third most common cancer worldwide and the second regarding number of deaths. In order to make a correct and early diagnosis to predict metastasis formation, biomarkers are an important tool. Although there are multiple signaling pathways associated with [...] Read more.
Colorectal cancer (CRC) comprises the third most common cancer worldwide and the second regarding number of deaths. In order to make a correct and early diagnosis to predict metastasis formation, biomarkers are an important tool. Although there are multiple signaling pathways associated with cancer progression, the most recognized are the MAPK pathway, p53 pathway, and TGF-β pathway. These pathways regulate many important functions in the cell, such as cell cycle regulation, proliferation, differentiation, and metastasis formation, among others. Changes in expression in genes belonging to these pathways are drivers of carcinogenesis. Often these expression changes are caused by mutations; however, epigenetic changes, such as DNA methylation, are increasingly acknowledged to play a role in the deregulation of oncogenic genes. This makes DNA methylation changes an interesting biomarkers in cancer. Among the newly identified biomarkers for CRC metastasis INHBB, SMOC2, BDNF, and TBRG4 are included, all of which are highly deregulated by methylation and closely associated with metastasis. The identification of such biomarkers in metastasis of CRC may allow a better treatment and early identification of cancer formation in order to perform better diagnostics and improve the life expectancy. Full article
(This article belongs to the Special Issue Biomarkers in Cancer)
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Article
Real-World Diagnostic Accuracy and Use of Immunohistochemical Markers in Lung Cancer Diagnostics
Biomolecules 2021, 11(11), 1721; https://doi.org/10.3390/biom11111721 - 18 Nov 2021
Cited by 1 | Viewed by 570
Abstract
Objectives: Accurate and reliable diagnostics are crucial as histopathological type influences selection of treatment in lung cancer. The aim of this study was to evaluate real-world accuracy and use of immunohistochemical (IHC) staining in lung cancer diagnostics. Materials and Methods: The diagnosis and [...] Read more.
Objectives: Accurate and reliable diagnostics are crucial as histopathological type influences selection of treatment in lung cancer. The aim of this study was to evaluate real-world accuracy and use of immunohistochemical (IHC) staining in lung cancer diagnostics. Materials and Methods: The diagnosis and used IHC stains for small specimens with lung cancer on follow-up resection were retrospectively investigated for a 15-month period at two major sites in Sweden. Additionally, 10 pathologists individually suggested diagnostic IHC staining for 15 scanned bronchial and lung biopsies and cytological specimens. Results: In 16 (4.7%) of 338 lung cancer cases, a discordant diagnosis of potential clinical relevance was seen between a small specimen and the follow-up resection. In half of the cases, there was a different small specimen from the same investigational work-up with a concordant diagnosis. Diagnostic inaccuracy was often related to a squamous marker not included in the IHC panel (also seen for the scanned cases), the case being a neuroendocrine tumor, thyroid transcription factor-1 (TTF-1) expression in squamous cell carcinomas (with clone SPT24), or poor differentiation. IHC was used in about 95% of cases, with a higher number of stains in biopsies and in squamous cell carcinomas and especially neuroendocrine tumors. Pre-surgical transthoracic samples were more often diagnostic than bronchoscopic ones (72–85% vs. 9–53% for prevalent types). Conclusions: Although a high overall diagnostic accuracy of small specimens was seen, small changes in routine practice (such as consequent inclusion of p40 and TTF-1 clone 8G7G3/1 in the IHC panel for non-small cell cancer with unclear morphology) may lead to improvement, while reducing the number of IHC stains would be preferable from a time and cost perspective. Full article
(This article belongs to the Special Issue Tumors of the Lungs and Pleura)
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Review
Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology
Biomolecules 2021, 11(11), 1720; https://doi.org/10.3390/biom11111720 - 18 Nov 2021
Cited by 3 | Viewed by 650
Abstract
Galectin-7 is a soluble unglycosylated lectin that is able to bind specifically to β-galactosides. It has been described to be involved in apoptosis, proliferation and differentiation, but also in cell adhesion and migration. Several disorders and diseases are discussed by covering the aforementioned [...] Read more.
Galectin-7 is a soluble unglycosylated lectin that is able to bind specifically to β-galactosides. It has been described to be involved in apoptosis, proliferation and differentiation, but also in cell adhesion and migration. Several disorders and diseases are discussed by covering the aforementioned biological processes. Structural features of galectin-7 are discussed as well as targeting the protein intracellularly or extracellularly. The exact molecular mechanisms that lie behind many biological processes involving galectin-7 are not known. It is therefore useful to come up with chemical probes or tools in order to obtain knowledge of the physiological processes. The objective of this review is to summarize the roles and functions of galectin-7 in the human body, providing reasons why it is necessary to design inhibitors for galectin-7, to give the reader structural insights and describe its current inhibitors. Full article
(This article belongs to the Special Issue Cell Biology of Galectins)
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Review
Transcription Factors in Alkaloid Engineering
Biomolecules 2021, 11(11), 1719; https://doi.org/10.3390/biom11111719 - 18 Nov 2021
Cited by 1 | Viewed by 839
Abstract
Plants produce a large variety of low-molecular-weight and specialized secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used in the pharmaceutical industry. Although alkaloid chemistry has been intensively investigated, characterization of alkaloid biosynthesis, including biosynthetic enzyme genes [...] Read more.
Plants produce a large variety of low-molecular-weight and specialized secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used in the pharmaceutical industry. Although alkaloid chemistry has been intensively investigated, characterization of alkaloid biosynthesis, including biosynthetic enzyme genes and their regulation, especially the transcription factors involved, has been relatively delayed, since only a limited number of plant species produce these specific types of alkaloids in a tissue/cell-specific or developmental-specific manner. Recent advances in molecular biology technologies, such as RNA sequencing, co-expression analysis of transcripts and metabolites, and functional characterization of genes using recombinant technology and cutting-edge technology for metabolite identification, have enabled a more detailed characterization of alkaloid pathways. Thus, transcriptional regulation of alkaloid biosynthesis by transcription factors, such as basic helix–loop–helix (bHLH), APETALA2/ethylene-responsive factor (AP2/ERF), and WRKY, is well elucidated. In addition, jasmonate signaling, an important cue in alkaloid biosynthesis, and its cascade, interaction of transcription factors, and post-transcriptional regulation are also characterized and show cell/tissue-specific or developmental regulation. Furthermore, current sequencing technology provides more information on the genome structure of alkaloid-producing plants with large and complex genomes, for genome-wide characterization. Based on the latest information, we discuss the application of transcription factors in alkaloid engineering. Full article
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Article
A Novel miRNA Screen Identifies miRNA-4454 as a Candidate Biomarker for Ventricular Fibrosis in Patients with Hypertrophic Cardiomyopathy
Biomolecules 2021, 11(11), 1718; https://doi.org/10.3390/biom11111718 - 18 Nov 2021
Cited by 2 | Viewed by 584
Abstract
(1) Background: Left ventricular hypertrophy, myocardial disarray and interstitial fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve the early detection of HCM. Circulating miRNAs have [...] Read more.
(1) Background: Left ventricular hypertrophy, myocardial disarray and interstitial fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve the early detection of HCM. Circulating miRNAs have been found to reflect disease processes in several cardiovascular diseases. (2) Methods: We quantified circulating miRNA molecules in the plasma of 24 HCM and 11 healthy controls using the Human v3 miRNA Expression Assay Kit Code set (Nanostring Tech., Seattle, WA, USA) and validated differentially expressed miRNAs using RT-PCR. (3) Results: In comparison to healthy controls, the levels of six miRNAs (miR-1, miR-3144, miR-4454, miR-495-3p, miR-499a-5p and miR-627-3p) were higher in the plasma of HCM patients than healthy individuals (p < 0.05). Of these, higher levels of miR-1, miR-495 and miR-4454 could be validated by real-time PCR. In addition, elevated miR-4454 levels were significantly correlated with cardiac fibrosis, detected by magnetic resonance imaging in HCM patients. (4) Conclusions: Circulating miR-1, miR-495-3p and miR-4454 levels are elevated in the plasma of HCM patients. To the best of our knowledge, this is the first report showing a correlation between miR-4454 levels and cardiac fibrosis in HCM. This suggests miR-4454 as a potential biomarker for fibrosis in these patients. Full article
(This article belongs to the Section Biomacromolecules: Nucleic Acids)
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Article
Probing the Metabolic Landscape of Plant Vascular Bundles by Infrared Fingerprint Analysis, Imaging and Mass Spectrometry
Biomolecules 2021, 11(11), 1717; https://doi.org/10.3390/biom11111717 - 18 Nov 2021
Cited by 1 | Viewed by 547
Abstract
Fingerprint analysis is a common technique in forensic and criminal investigations. Similar techniques exist in the field of infrared spectroscopy to identify biomolecules according to their characteristic spectral fingerprint features. These unique markers are located in a wavenumber range from 1800 to 600 [...] Read more.
Fingerprint analysis is a common technique in forensic and criminal investigations. Similar techniques exist in the field of infrared spectroscopy to identify biomolecules according to their characteristic spectral fingerprint features. These unique markers are located in a wavenumber range from 1800 to 600 cm−1 in the mid infrared region. Here, a novel bioanalytical concept of correlating these spectral features with corresponding mass spectrometry datasets to unravel metabolic clusters within complex plant tissues was applied. As proof of concept, vascular bundles of oilseed rape (Brassica napus) were investigated, one of the most important and widely cultivated temperate zone oilseed crops. The link between mass spectrometry data and spectral data identified features that co-aligned within both datasets. Regions of origin were then detected by searching for these features in hyperspectral images of plant tissues. This approach, based on co-alignment and co-localization, finally enabled the detection of eight distinct metabolic clusters, reflecting functional and structural arrangements within the vascular bundle. The proposed analytical concept may assist future synergistic research approaches and may lead to biotechnological innovations with regard to crop yield and sustainability. Full article
(This article belongs to the Collection Feature Papers in Biochemistry)
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Review
D-Amino Acids and D-Amino Acid-Containing Peptides: Potential Disease Biomarkers and Therapeutic Targets?
Biomolecules 2021, 11(11), 1716; https://doi.org/10.3390/biom11111716 - 18 Nov 2021
Cited by 6 | Viewed by 1048
Abstract
In nature, amino acids are found in two forms, L and D enantiomers, except for glycine which does not have a chiral center. The change of one form to the other will lead to a change in the primary structure of proteins and [...] Read more.
In nature, amino acids are found in two forms, L and D enantiomers, except for glycine which does not have a chiral center. The change of one form to the other will lead to a change in the primary structure of proteins and hence may affect the function and biological activity of proteins. Indeed, several D-amino acid-containing peptides (DAACPs) were isolated from patients with cataracts, Alzheimer’s and other diseases. Additionally, significant levels of free D-amino acids were found in several diseases, reflecting the disease conditions. Studying the molecular mechanisms of the DAACPs formation and the alteration in D-amino acids metabolism will certainly assist in understanding these diseases and finding new biomarkers and drug targets. In this review, the presence of DAACPs and free D-amino acids and their links with disease development and progress are summarized. Similarly, we highlight some recent advances in analytical techniques that led to improvement in the discovery and analysis of DAACPs and D-amino acids. Full article
(This article belongs to the Section Biomacromolecules: Proteins)
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Article
Extracellular Polymeric Substances Facilitate the Adsorption and Migration of Cu2+ and Cd2+ in Saturated Porous Media
Biomolecules 2021, 11(11), 1715; https://doi.org/10.3390/biom11111715 - 17 Nov 2021
Cited by 1 | Viewed by 639
Abstract
Heavy metal contamination in groundwater is a serious environmental problem. Many microorganisms that survive in subsurface porous media also produce extracellular polymeric substances (EPS), but little is known about the effect of these EPS on the fate and transport of heavy metals in [...] Read more.
Heavy metal contamination in groundwater is a serious environmental problem. Many microorganisms that survive in subsurface porous media also produce extracellular polymeric substances (EPS), but little is known about the effect of these EPS on the fate and transport of heavy metals in aquifers. In this study, EPS extracted from soil with a steam method were used to study the adsorption behaviors of Cu2+ and Cd2+, employing quartz sand as a subsurface porous medium. The results showed that EPS had a good adsorption capacity for Cu2+ (13.5 mg/g) and Cd2+ (14.1 mg/g) that can be viewed using the Temkin and Freundlich models, respectively. At a pH value of 6.5 ± 0.1 and a temperature of 20 °C, EPS showed a greater affinity for Cu2+ than for Cd2+. The binding force between EPS and quartz sand was weak. The prior saturation of the sand media with EPS solution can significantly promote the migration of the Cu2+ and Cd2+ in sand columns by 8.8% and 32.1%, respectively. When treating both metals simultaneously, the migration of Cd2+ was found to be greater than that of Cu2+. This also demonstrated that EPS can promote the co-migration of Cu2+ and Cd2+ in saturated porous media. Full article
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Article
Porphyrin Molecules Decorated on Metal-Organic Frameworks for Multi-Functional Biomedical Applications
Biomolecules 2021, 11(11), 1714; https://doi.org/10.3390/biom11111714 - 17 Nov 2021
Cited by 5 | Viewed by 1580
Abstract
Metal–organic frameworks (MOFs) have been widely used as porous nanomaterials for different applications ranging from industrial to biomedicals. An unpredictable one-pot method is introduced to synthesize NH2-MIL-53 assisted by high-gravity in a greener media for the first time. Then, porphyrins were [...] Read more.
Metal–organic frameworks (MOFs) have been widely used as porous nanomaterials for different applications ranging from industrial to biomedicals. An unpredictable one-pot method is introduced to synthesize NH2-MIL-53 assisted by high-gravity in a greener media for the first time. Then, porphyrins were deployed to adorn the surface of MOF to increase the sensitivity of the prepared nanocomposite to the genetic materials and in-situ cellular protein structures. The hydrogen bond formation between genetic domains and the porphyrin’ nitrogen as well as the surface hydroxyl groups is equally probable and could be considered a milestone in chemical physics and physical chemistry for biomedical applications. In this context, the role of incorporating different forms of porphyrins, their relationship with the final surface morphology, and their drug/gene loading efficiency were investigated to provide a predictable pattern in regard to the previous works. The conceptual phenomenon was optimized to increase the interactions between the biomolecules and the substrate by reaching the limit of detection to 10 pM for the Anti-cas9 protein, 20 pM for the single-stranded DNA (ssDNA), below 10 pM for the single guide RNA (sgRNA) and also around 10 nM for recombinant SARS-CoV-2 spike antigen. Also, the MTT assay showed acceptable relative cell viability of more than 85% in most cases, even by increasing the dose of the prepared nanostructures. Full article
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Review
Rare Does Not Mean Worthless: How Rare Diseases Have Shaped Neurodevelopment Research in the NGS Era
Biomolecules 2021, 11(11), 1713; https://doi.org/10.3390/biom11111713 - 17 Nov 2021
Viewed by 796
Abstract
The advent of next-generation sequencing (NGS) is heavily changing both the diagnosis of human conditions and basic biological research. It is now possible to dig deep inside the genome of hundreds of thousands or even millions of people and find both common and [...] Read more.
The advent of next-generation sequencing (NGS) is heavily changing both the diagnosis of human conditions and basic biological research. It is now possible to dig deep inside the genome of hundreds of thousands or even millions of people and find both common and rare genomic variants and to perform detailed phenotypic characterizations of both physiological organs and experimental models. Recent years have seen the introduction of multiple techniques using NGS to profile transcription, DNA and chromatin modifications, protein binding, etc., that are now allowing us to profile cells in bulk or even at a single-cell level. Although rare and ultra-rare diseases only affect a few people, each of these diseases represent scholarly cases from which a great deal can be learned about the pathological and physiological function of genes, pathways, and mechanisms. Therefore, for rare diseases, state-of-the-art investigations using NGS have double valence: their genomic cause (new variants) and the characterize the underlining the mechanisms associated with them (discovery of gene function) can be found. In a non-exhaustive manner, this review will outline the main usage of NGS-based techniques for the diagnosis and characterization of neurodevelopmental disorders (NDDs), under whose umbrella many rare and ultra-rare diseases fall. Full article
(This article belongs to the Special Issue Advance in Genomics of Rare Genetic Diseases)
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