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Biomolecules, Volume 10, Issue 2 (February 2020) – 175 articles

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Open AccessArticle
Acorus gramineusand and Euodia ruticarpa Steam Distilled Essential Oils Exert Anti-Inflammatory Effects Through Decreasing Th1/Th2 and Pro-/Anti-Inflammatory Cytokine Secretion Ratios In Vitro
Biomolecules 2020, 10(2), 338; https://doi.org/10.3390/biom10020338 (registering DOI) - 19 Feb 2020
Abstract
To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary [...] Read more.
To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary splenocytes and peritoneal macrophages. T helper type 1 lymphocytes (Th1) (IL-2), Th2 (IL-5), pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines secreted by correspondent immune cells treated with SDEO samples were determined using enzyme-linked immunosorbent assay. The total amounts of potential phytochemicals, including total flavonoids, polyphenols and saponins, in these two selected SDEOs were measured and correlated with cytokine levels secreted by immune cells. Our results evidenced that ER SDEO is rich in total flavonoids, polyphenols and saponins. Treatments with AG and ER SDEO significantly (p < 0.05) increased IL-5/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, suggesting that both AG and ER SDEO have the Th2-polarization property and anti-inflammatory potential. In addition, AG and ER SDEO, particularly ER SDEO, markedly decreased TNF-α/IL-10 secretion ratios by macrophages in the absence or presence of lipopolysaccharide (LPS), exhibiting substantial effects on spontaneous and LPS-induced inflammation. Significant correlations were found between the total polyphenols, flavonoids or saponins content in the two selected SDEOs and Th1/Th2 immune balance or anti-inflammatory ability in linear, non-linear or biphasic manners, respectively. In conclusion, our results suggest that AG and ER, particularly ER, SDEO have immunomodulatory potential in shifting the Th1/Th2 balance toward Th2 polarization in splenocytes and inhibiting inflammation in macrophages in the absence or presence of LPS. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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Open AccessReview
Pathological Crosstalk between Metastatic Breast Cancer Cells and the Bone Microenvironment
Biomolecules 2020, 10(2), 337; https://doi.org/10.3390/biom10020337 (registering DOI) - 19 Feb 2020
Abstract
Bone is the most common metastatic site in breast cancer. Upon arrival to the bone, disseminated tumor cells can undergo a period of dormancy but often eventually grow and hijack the bone microenvironment. The bone marrow microenvironment consists of multiple cell types including [...] Read more.
Bone is the most common metastatic site in breast cancer. Upon arrival to the bone, disseminated tumor cells can undergo a period of dormancy but often eventually grow and hijack the bone microenvironment. The bone marrow microenvironment consists of multiple cell types including the bone cells, adipocytes, endothelial cells, and nerve cells that all have crucial functions in the maintenance of bone homeostasis. Tumor cells severely disturb the tightly controlled cellular and molecular interactions in the bone marrow fueling their own survival and growth. While the role of bone resorbing osteoclasts in breast cancer bone metastases is well established, the function of other bone cells, as well as adipocytes, endothelial cells, and nerve cells is less understood. In this review, we discuss the composition of the physiological bone microenvironment and how the presence of tumor cells influences the microenvironment, creating a pathological crosstalk between the cells. A better understanding of the cellular and molecular events that occur in the metastatic bone microenvironment could facilitate the identification of novel cellular targets to treat this devastating disease. Full article
(This article belongs to the Special Issue Connecting the Bone with Other Organs: A Reciprocal Cross-Talk)
Open AccessArticle
Cinnamomum verum Bark Extract Mediated Green Synthesis of ZnO Nanoparticles and Their Antibacterial Potentiality
Biomolecules 2020, 10(2), 336; https://doi.org/10.3390/biom10020336 (registering DOI) - 19 Feb 2020
Abstract
Cinnamomum verum plant extract mediated propellant chemistry route was used for the green synthesis of zinc oxide nanoparticles. Prepared samples were confirmed for their nano regime using advanced characterization techniques such as powder X-ray diffraction and microscopic techniques such as scanning electron microscopy [...] Read more.
Cinnamomum verum plant extract mediated propellant chemistry route was used for the green synthesis of zinc oxide nanoparticles. Prepared samples were confirmed for their nano regime using advanced characterization techniques such as powder X-ray diffraction and microscopic techniques such as scanning electron microscopy and transmission electron microscopy. The energy band gap of the green synthesized zinc oxide (ZnO)-nanoparticles (NPs) were found between 3.25–3.28 eV. Fourier transmission infrared spectroscopy shows the presence of Zn-O bond within the wave number of 500 cm−1. SEM images show the specific agglomeration of particles which was also confirmed by TEM studies. The green synthesized ZnO-NPs inhibited the growth of Escherichia coli and Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 125 µg mL−1 and 62.5 µg mL−1, respectively. The results indicate the prepared ZnO-NPs can be used as a potential antimicrobial agent against harmful pathogens. Full article
Open AccessReview
The Challenge of Disease-Modifying Therapies in Parkinson’s Disease: Role of CSF Biomarkers
Biomolecules 2020, 10(2), 335; https://doi.org/10.3390/biom10020335 (registering DOI) - 19 Feb 2020
Abstract
The development of disease modifying strategies in Parkinson’s disease (PD) largely depends on the ability to identify suitable populations after accurate diagnostic work-up. Therefore, patient molecular profiling and disease subtyping are mandatory. Thus far, in clinical trials, PD has been considered to be [...] Read more.
The development of disease modifying strategies in Parkinson’s disease (PD) largely depends on the ability to identify suitable populations after accurate diagnostic work-up. Therefore, patient molecular profiling and disease subtyping are mandatory. Thus far, in clinical trials, PD has been considered to be a “single entity”. Conversely, in front of the common feature of nigro-striatal degeneration, PD is pathogenically heterogeneous with a series of several biological and molecular pathways that differently contribute to clinical development and progression. Currently available diagnostic criteria for PD mainly rely on clinical features and imaging biomarkers, thus missing to identify the contribution of pathophysiological pathways, also failing to catch abnormalities occurring in the early stages of disease. Cerebrospinal fluid (CSF) is a promising source of biomarkers, with the high potential for reflecting early changes occurring in PD brain. In this review, we provide an overview on CSF biomarkers in PD, discussing their association with different molecular pathways involved either in pathophysiology or progression in detail. Their potential application in the field of disease modifying treatments is also discussed. Full article
Open AccessArticle
Anti-Infectives Restore ORKAMBI® Rescue of F508del-CFTR Function in Human Bronchial Epithelial Cells Infected with Clinical Strains of P. aeruginosa
Biomolecules 2020, 10(2), 334; https://doi.org/10.3390/biom10020334 (registering DOI) - 19 Feb 2020
Abstract
Chronic infection and inflammation are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. ORKAMBI® (Lumacaftor-Ivacaftor) is an approved combination therapy for Cystic Fibrosis (CF) patients bearing the most common mutation, F508del, in the cystic fibrosis conductance regulator (CFTR) [...] Read more.
Chronic infection and inflammation are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. ORKAMBI® (Lumacaftor-Ivacaftor) is an approved combination therapy for Cystic Fibrosis (CF) patients bearing the most common mutation, F508del, in the cystic fibrosis conductance regulator (CFTR) protein. It has been previously shown that ORKAMBI®-mediated rescue of CFTR is reduced by a pre-existing Pseudomonas aeruginosa infection. Here, we show that the infection of F508del-CFTR human bronchial epithelial (HBE) cells with lab strain and four different clinical strains of P. aeruginosa, isolated from the lung sputum of CF patients, decreases CFTR function in a strain-specific manner by 48 to 88%. The treatment of infected cells with antibiotic tobramycin or cationic antimicrobial peptide 6K-F17 was found to decrease clinical strain bacterial growth on HBE cells and restore ORKAMBI®-mediated rescue of F508del-CFTR function. Further, 6K-F17 was found to downregulate the expression of pro-inflammatory cytokines, interleukin (IL)-8, IL-6, and tumor necrosis factor-α in infected HBE cells. The results provide strong evidence for a combination therapy approach involving CFTR modulators and anti-infectives (i.e., tobramycin and/or 6K-F17) to improve their overall efficacy in CF patients. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle
Characterization of a Novel Mannose-Binding Lectin with Antiviral Activities from Red Alga, Grateloupia chiangii
Biomolecules 2020, 10(2), 333; https://doi.org/10.3390/biom10020333 (registering DOI) - 19 Feb 2020
Abstract
Lectins have the ability to bind specific carbohydrates and they have potential applications as medical and pharmacological agents. The unique structure and usefulness of red algal lectin have been reported, but these lectins are limited to a few marine algal groups. In this [...] Read more.
Lectins have the ability to bind specific carbohydrates and they have potential applications as medical and pharmacological agents. The unique structure and usefulness of red algal lectin have been reported, but these lectins are limited to a few marine algal groups. In this study, a novel mannose-binding lectin from Grateloupia chiangii (G. chiangii lectin, GCL) was purified using antiviral screens and affinity chromatography. We characterized the molecular weight, agglutination activity, hemagglutination activity, and heat stability of GCL. To determine the carbohydrate specificity, a glycan microarray was performed. GCL showed strong binding affinity for Maltohexaose-β-Sp1 and Maltoheptaose-β-Sp1 with weak affinity for other monosaccharides and preferred binding to high-mannan structures. The N-terminal sequence and peptide sequence of GCL were determined using an Edman degradation method and LC-MS/MS, and the cDNA and peptide sequences were deduced. GCL was shown to consist of 231 amino acids (24.9 kDa) and the N-terminus methionine was eliminated after translation. GCL possessed a tandem repeat structure of six domains, similar to the other red algal lectins. The mannose binding properties and tandem repeat structure of GCL may confer it the potential to act as an antiviral agent for protection against viral infection. Full article
(This article belongs to the Section Biomacromolecules)
Open AccessFeature PaperReview
Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis
Biomolecules 2020, 10(2), 332; https://doi.org/10.3390/biom10020332 (registering DOI) - 19 Feb 2020
Abstract
Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes [...] Read more.
Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes and chondrocytes. Moreover, human genetic mutations in Notch components emphasize the critical roles of Notch signaling in skeletal development and homeostasis. In this review, we focus on the physiological roles of Notch signaling in skeletogenesis, postnatal bone and cartilage homeostasis and fracture repair. We also discuss the pathological gain- and loss-of-function of Notch signaling in bone and cartilage, resulting in osteosarcoma and age-related degenerative diseases, such as osteoporosis and osteoarthritis. Understanding the physiological and pathological function of Notch signaling in skeletal tissues using animal models and human genetics will provide new insights into disease pathogenesis and offer novel approaches for the treatment of bone/cartilage diseases. Full article
Open AccessEditorial
Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity
Biomolecules 2020, 10(2), 331; https://doi.org/10.3390/biom10020331 (registering DOI) - 19 Feb 2020
Abstract
The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential [...] Read more.
The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins. Full article
Open AccessReview
NAD+ Metabolism and Regulation: Lessons from Yeast
Biomolecules 2020, 10(2), 330; https://doi.org/10.3390/biom10020330 (registering DOI) - 19 Feb 2020
Abstract
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite involved in various cellular processes. The cellular NAD+ pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human. NAD+ metabolism is an emerging therapeutic target for [...] Read more.
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite involved in various cellular processes. The cellular NAD+ pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human. NAD+ metabolism is an emerging therapeutic target for several human disorders including diabetes, cancer, and neuron degeneration. Factors regulating NAD+ homeostasis have remained incompletely understood due to the dynamic nature and complexity of NAD+ metabolism. Recent studies using the genetically tractable budding yeast Saccharomyces cerevisiae have identified novel NAD+ homeostasis factors. These findings help provide a molecular basis for how may NAD+ and NAD+ homeostasis factors contribute to the maintenance and regulation of cellular function. Here we summarize major NAD+ biosynthesis pathways, selected cellular processes that closely connect with and contribute to NAD+ homeostasis, and regulation of NAD+ metabolism by nutrient-sensing signaling pathways. We also extend the discussions to include possible implications of NAD+ homeostasis factors in human disorders. Understanding the cross-regulation and interconnections of NAD+ precursors and associated cellular pathways will help elucidate the mechanisms of the complex regulation of NAD+ homeostasis. These studies may also contribute to the development of effective NAD+-based therapeutic strategies specific for different types of NAD+ deficiency related disorders. Full article
(This article belongs to the Special Issue Nicotinamide in Health and Diseases)
Open AccessArticle
Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells from Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy
Biomolecules 2020, 10(2), 329; https://doi.org/10.3390/biom10020329 (registering DOI) - 19 Feb 2020
Abstract
Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component, but the presence of environmental stressors can be important for its onset and progression. Cannabis use can be a major risk factor for developing SCZ. However, despite the available data on the [...] Read more.
Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component, but the presence of environmental stressors can be important for its onset and progression. Cannabis use can be a major risk factor for developing SCZ. However, despite the available data on the neurobiological underpinnings of SCZ, there is an important lack of studies in human neuronal tissue and living cells addressing the effects of cannabis in SCZ patients. In this study, we analysed the most relevant bio-macromolecular constituents in olfactory neuroepithelium (ON) cells of healthy controls non-cannabis users, healthy cannabis users, SCZ patients non-cannabis users, and SCZ patients cannabis users using Synchrotron Radiation-Fourier Transform Infrared (SR-FTIR) spectrometry and microscopy. Our results revealed that SCZ patients non-cannabis users, and healthy cannabis users exhibit similar alterations in the macromolecular profile of ON cells, including disruption in lipid composition, increased lipid membrane renewal rate and lipid peroxidation, altered proteins containing more β-sheet structures, and showed an increase in DNA and histone methylation. Notably, these alterations were not observed in SCZ patients who use cannabis regularly. These data suggest a differential effect of cannabis in healthy controls and in SCZ patients in terms of the macromolecular constituents of ON cells. Full article
(This article belongs to the Special Issue The Endocannabinoid System in Health and Disease)
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Open AccessArticle
Seasonal and Antioxidant Evaluation of Essential Oil from Eugenia uniflora L., Curzerene-Rich, Thermally Produced in Situ
Biomolecules 2020, 10(2), 328; https://doi.org/10.3390/biom10020328 (registering DOI) - 19 Feb 2020
Abstract
The essential oil of Eugenia uniflora has been attributed anti-depressive, antinociceptive, antileishmanial, larvicidal, antioxidant, antibacterial, and antifungal activities. It is known that the cultivation of this plant can be affected by seasonality, promoting alteration in the oil composition and its biological activities. This [...] Read more.
The essential oil of Eugenia uniflora has been attributed anti-depressive, antinociceptive, antileishmanial, larvicidal, antioxidant, antibacterial, and antifungal activities. It is known that the cultivation of this plant can be affected by seasonality, promoting alteration in the oil composition and its biological activities. This study aims to perform the annual evaluation of the curzerene-type oil of E. uniflora and determine its antioxidant activity. The oil yield from the dry season (1.4 ± 0.6%) did not differ statistically from that of the rainy season (1.8 ± 0.8%). Curzerene, an oxygenated sesquiterpene, was the principal constituent, and its percentage showed no significant difference between the two periods: dry (42.7% ± 6.1) and rainy (40.8 ± 5.9%). Principal component and hierarchical cluster analyses presented a high level of similarity between the monthly samples of the oils. Also, in the annual study, the yield and composition of the oils did not present a significant correlation with the climatic variables. The antioxidant activity of the oils showed inhibition of DPPH radicals with an average value of 55.0 ± 6.6%. The high curzerene content in the monthly oils of E. uniflora suggests their potential for use as a future phytotherapeutic alternative. Full article
(This article belongs to the Special Issue Perspectives of Essential Oils)
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Open AccessArticle
Characterization of the CRM Gene Family and Elucidating the Function of OsCFM2 in Rice
Biomolecules 2020, 10(2), 327; https://doi.org/10.3390/biom10020327 (registering DOI) - 18 Feb 2020
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Abstract
The chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins regulate the expression of chloroplast or mitochondrial genes that influence plant growth and development. Although 14 CRM domain proteins have previously been identified in rice, there are few studies of these gene expression [...] Read more.
The chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins regulate the expression of chloroplast or mitochondrial genes that influence plant growth and development. Although 14 CRM domain proteins have previously been identified in rice, there are few studies of these gene expression patterns in various tissues and under abiotic stress. In our study, we found that 14 CRM domain-containing proteins have a conservative motif1. Under salt stress, the expression levels of 14 CRM genes were downregulated. However, under drought and cold stress, the expression level of some CRM genes was increased. The analysis of gene expression patterns showed that 14 CRM genes were expressed in all tissues but especially highly expressed in leaves. In addition, we analyzed the functions of OsCFM2 and found that this protein influences chloroplast development by regulating the splicing of a group I and five group II introns. Our study provides information for the function analysis of CRM domain-containing proteins in rice. Full article
(This article belongs to the Section Molecular Biology)
Open AccessArticle
Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma
Biomolecules 2020, 10(2), 326; https://doi.org/10.3390/biom10020326 (registering DOI) - 18 Feb 2020
Viewed by 117
Abstract
Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this [...] Read more.
Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this study, we focused on protein phosphatase 2A (PP2A), a key factor regulating glucocorticoid receptor (GR) nuclear translocation, and examined its association with local responses to corticosteroids in eosinophilic airway inflammation. Our results indicated reduced responses to corticosteroids in nasal epithelial cells from ECRS patients with asthma, which were also associated with decreased PP2A mRNA expression. Eosinophil peroxidase stimulates elevated PP2A phosphorylation levels, reducing PP2A protein expression and activity. In addition, mRNA levels of inflammatory mediators (TSLP, IL-25, IL-33, CCL4, CCL5, CCL11, and CCL26) associated with eosinophilic airway inflammation in epithelial cells were increased in nasal polyps (eosinophil-rich areas) compared with those in uncinate process tissues (eosinophil-poor areas) from the same patients. PP2A reduction by siRNA reduced GR nuclear translocation, whereas PP2A overexpression by plasmid transfection, or PP2A activation by formoterol, enhanced GR nuclear translocation. Collectively, our findings indicate that PP2A may represent a promising therapeutic target in refractory eosinophilic airway inflammation characterized by local steroid insensitivity. Full article
(This article belongs to the Special Issue Eosinophilic Inflammation)
Open AccessFeature PaperReview
Current Advances in Allosteric Modulation of Muscarinic Receptors
Biomolecules 2020, 10(2), 325; https://doi.org/10.3390/biom10020325 (registering DOI) - 18 Feb 2020
Viewed by 82
Abstract
Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter. Allosteric modulators modulate the binding affinity, potency, and efficacy of orthosteric ligands. Muscarinic acetylcholine receptors are prototypical allosterically-modulated [...] Read more.
Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter. Allosteric modulators modulate the binding affinity, potency, and efficacy of orthosteric ligands. Muscarinic acetylcholine receptors are prototypical allosterically-modulated G-protein-coupled receptors. They are a potential therapeutic target for the treatment of psychiatric, neurologic, and internal diseases like schizophrenia, Alzheimer’s disease, Huntington disease, type 2 diabetes, or chronic pulmonary obstruction. Here, we reviewed the progress made during the last decade in our understanding of their mechanisms of binding, allosteric modulation, and in vivo actions in order to understand the translational impact of studying this important class of pharmacological agents. We overviewed newly developed allosteric modulators of muscarinic receptors as well as new spin-off ideas like bitopic ligands combining allosteric and orthosteric moieties and photo-switchable ligands based on bitopic agents. Full article
Open AccessArticle
2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from Inula britannica Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
Biomolecules 2020, 10(2), 324; https://doi.org/10.3390/biom10020324 (registering DOI) - 18 Feb 2020
Viewed by 87
Abstract
2α-Hydroxyeudesma-4,11(13)-dien-8β,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from Inula britannica, displays cytotoxic activity against diffuse large B cell lymphoma cells in vitro. However, the molecular mechanism of the anticancer effect remains unclear. In this study, [...] Read more.
2α-Hydroxyeudesma-4,11(13)-dien-8β,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from Inula britannica, displays cytotoxic activity against diffuse large B cell lymphoma cells in vitro. However, the molecular mechanism of the anticancer effect remains unclear. In this study, we showed that HEDO inhibits cell growth by inducing apoptosis in lymphoma cell lines through its antiproliferative activity. HEDO increases the depolarization of mitochondrial membrane potential and upregulated intracellular reactive oxygen species (ROS). Furthermore, we examined the cell cycle effect, and our results provided evidence that the arrest of the cell cycle at the SubG0/G1 phase plays an important role in the ability of HEDO to inhibit cell growth in Ontario Cancer Institute (OCI)-LY3 lymphoma cells by preventing nuclear factor-kappa B (NF-κB) signaling. In addition, HEDO induced apoptosis by instigating the activation of Bcl-2-associated X (BAX) and cleaved caspase-3, decreasing B-cell lymphoma 2 (BCL2), B-cell lymphoma-extra large (BCL-XL), and procaspase 3 expression levels. Based on these findings, we suggest that HEDO has potential as an anticancer drug of lymphoma by inducing ROS-dependent accumulation of SubG0/G1 arrest and apoptosis in OCI-LY3 cells. Full article
(This article belongs to the Special Issue Antitumor Agents from Natural Sources)
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Open AccessReview
Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors
Biomolecules 2020, 10(2), 323; https://doi.org/10.3390/biom10020323 (registering DOI) - 18 Feb 2020
Viewed by 112
Abstract
Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2 [...] Read more.
Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2S donors have been found to be effective in the prevention of gastrointestinal ulcers during anti-inflammatory treatment. Notably, there are well-established medicines used for the treatment of a variety of diseases, whose chemical structure contains sulfur moieties and may release H2S. Hence, the therapeutic effect of these drugs may be partly the result of the release of H2S occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about H2S-dependent pharmacotherapeutic effects of these drugs. Full article
Open AccessArticle
Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast
Biomolecules 2020, 10(2), 322; https://doi.org/10.3390/biom10020322 (registering DOI) - 18 Feb 2020
Viewed by 89
Abstract
Modifications found in the Anticodon Stem Loop (ASL) of tRNAs play important roles in regulating translational speed and accuracy. Threonylcarbamoyl adenosine (t6A37) and 5-methoxycarbonyl methyl-2-thiouridine (mcm5s2U34) are critical ASL modifications that have been linked to several human [...] Read more.
Modifications found in the Anticodon Stem Loop (ASL) of tRNAs play important roles in regulating translational speed and accuracy. Threonylcarbamoyl adenosine (t6A37) and 5-methoxycarbonyl methyl-2-thiouridine (mcm5s2U34) are critical ASL modifications that have been linked to several human diseases. The model yeast Saccharomyces cerevisiae is viable despite the absence of both modifications, growth is however greatly impaired. The major observed consequence is a subsequent increase in protein aggregates and aberrant morphology. Proteomic analysis of the t6A-deficient strain (sua5 mutant) revealed a global mistranslation leading to protein aggregation without regard to physicochemical properties or t6A-dependent or biased codon usage in parent genes. However, loss of sua5 led to increased expression of soluble proteins for mitochondrial function, protein quality processing/trafficking, oxidative stress response, and energy homeostasis. These results point to a global function for t6A in protein homeostasis very similar to mcm5/s2U modifications. Full article
(This article belongs to the collection RNA Modifications)
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Open AccessArticle
The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity
Biomolecules 2020, 10(2), 321; https://doi.org/10.3390/biom10020321 (registering DOI) - 17 Feb 2020
Viewed by 150
Abstract
Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging [...] Read more.
Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1−/−) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1−/− and WT mice ingested similar chow and calories; however, the THOP1−/− mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1−/− mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1−/− fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1−/− mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously unanticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview
Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology
Biomolecules 2020, 10(2), 320; https://doi.org/10.3390/biom10020320 (registering DOI) - 17 Feb 2020
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Abstract
Reactive oxygen species (ROS) are byproducts of aerobic respiration and signaling molecules that control various cellular functions. Nrf2 governs the gene expression of endogenous antioxidant synthesis and ROS-eliminating enzymes in response to various electrophilic compounds that inactivate the negative regulator Keap1. Accumulating evidence [...] Read more.
Reactive oxygen species (ROS) are byproducts of aerobic respiration and signaling molecules that control various cellular functions. Nrf2 governs the gene expression of endogenous antioxidant synthesis and ROS-eliminating enzymes in response to various electrophilic compounds that inactivate the negative regulator Keap1. Accumulating evidence has shown that mitochondrial ROS (mtROS) activate Nrf2, often mediated by certain protein kinases, and induce the expression of antioxidant genes and genes involved in mitochondrial quality/quantity control. Mild physiological stress, such as caloric restriction and exercise, elicits beneficial effects through a process known as “mitohormesis.” Exercise induces NOX4 expression in the heart, which activates Nrf2 and increases endurance capacity. Mice transiently depleted of SOD2 or overexpressing skeletal muscle-specific UCP1 exhibit Nrf2-mediated antioxidant gene expression and PGC1α-mediated mitochondrial biogenesis. ATF4 activation may induce a transcriptional program that enhances NADPH synthesis in the mitochondria and might cooperate with the Nrf2 antioxidant system. In response to severe oxidative stress, Nrf2 induces Klf9 expression, which represses mtROS-eliminating enzymes to enhance cell death. Nrf2 is inactivated in certain pathological conditions, such as diabetes, but Keap1 down-regulation or mtROS elimination rescues Nrf2 expression and improves the pathology. These reports aid us in understanding the roles of Nrf2 in pathophysiological alterations involving mtROS. Full article
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Open AccessArticle
Role of Serum and Urine Biomarkers (PLA2R and THSD7A) in Diagnosis, Monitoring and Prognostication of Primary Membranous Glomerulonephritis
Biomolecules 2020, 10(2), 319; https://doi.org/10.3390/biom10020319 (registering DOI) - 17 Feb 2020
Viewed by 113
Abstract
Differentiating primary and secondary membranous glomerulonephritis (MGN) using biomarkers for MGN is essential in patients’ diagnosis, treatment and follow-up. Although biopsy has been the primary tool in making the diagnosis, not all patients can withstand it due to its invasive nature, and it [...] Read more.
Differentiating primary and secondary membranous glomerulonephritis (MGN) using biomarkers for MGN is essential in patients’ diagnosis, treatment and follow-up. Although biopsy has been the primary tool in making the diagnosis, not all patients can withstand it due to its invasive nature, and it cannot be used to monitor treatment. Hence, there is the need for less invasive or even non-invasive biomarkers for effective diagnosis, treatment monitoring and prognostication. This study aimed at providing an alternative way of differentiating primary and secondary MGN using enzyme-linked immunosorbent assay (ELISA) technique for serum and urine biomarkers (M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A)) for prompt diagnosis, treatment and prognosis. A total of 125 subjects, including 81 primary and 44 secondary MGN subjects, were diagnosed from January 2012 to October 2019 at Hospital Serdang and Hospital Kuala Lumpur from which 69 subjects consisting of 45 primary and 24 secondary MGN subjects participated in the study. Of these, 13 primary MGN subjects were positive for both serum and urine anti-PLA2R antibodies (Ab) whereas only one secondary MGN subject associated with hepatitis B virus was positive for both serum and urine anti-PLA2R Ab. At the same time, anti-THSD7A Ab was found positive in four primary MGN subjects and two secondary MGN subjects with malignancy. Full article
Open AccessArticle
Kernel Differential Subgraph Analysis to Reveal the Key Period Affecting Glioblastoma
Biomolecules 2020, 10(2), 318; https://doi.org/10.3390/biom10020318 (registering DOI) - 17 Feb 2020
Viewed by 104
Abstract
Glioblastoma (GBM) is a fast-growing type of malignant primary brain tumor. To explore the mechanisms in GBM, complex biological networks are used to reveal crucial changes among different biological states, which reflect on the development of living organisms. It is critical to discover [...] Read more.
Glioblastoma (GBM) is a fast-growing type of malignant primary brain tumor. To explore the mechanisms in GBM, complex biological networks are used to reveal crucial changes among different biological states, which reflect on the development of living organisms. It is critical to discover the kernel differential subgraph (KDS) that leads to drastic changes. However, identifying the KDS is similar to the Steiner Tree problem that is an NP-hard problem. In this paper, we developed a criterion to explore the KDS (CKDS), which considered the connectivity and scale of KDS, the topological difference of nodes and function relevance between genes in the KDS. The CKDS algorithm was applied to simulated datasets and three single-cell RNA sequencing (scRNA-seq) datasets including GBM, fetal human cortical neurons (FHCN) and neural differentiation. Then we performed the network topology and functional enrichment analyses on the extracted KDSs. Compared with the state-of-art methods, the CKDS algorithm outperformed on simulated datasets to discover the KDSs. In the GBM and FHCN, seventeen genes (one biomarker, nine regulatory genes, one driver genes, six therapeutic targets) and KEGG pathways in KDSs were strongly supported by literature mining that they were highly interrelated with GBM. Moreover, focused on GBM, there were fifteen genes (including ten regulatory genes, three driver genes, one biomarkers, one therapeutic target) and KEGG pathways found in the KDS of neural differentiation process from activated neural stem cells (aNSC) to neural progenitor cells (NPC), while few genes and no pathway were found in the period from NPC to astrocytes (Ast). These experiments indicated that the process from aNSC to NPC is a key differentiation period affecting the development of GBM. Therefore, the CKDS algorithm provides a unique perspective in identifying cell-type-specific genes and KDSs. Full article
Open AccessFeature PaperArticle
Generation and Characterization of a CRISPR/Cas9 -Induced 3-mst Deficient Zebrafish
Biomolecules 2020, 10(2), 317; https://doi.org/10.3390/biom10020317 (registering DOI) - 17 Feb 2020
Viewed by 146
Abstract
3-mercaptopyruvate sulfurtransferase (3-MST) is an enzyme capable of synthesizing hydrogen sulfide (H2S) and polysulfides. In spite of its ubiquitous presence in mammalian cells, very few studies have investigated its contribution to homeostasis and disease development, thus the role of 3-MST remains [...] Read more.
3-mercaptopyruvate sulfurtransferase (3-MST) is an enzyme capable of synthesizing hydrogen sulfide (H2S) and polysulfides. In spite of its ubiquitous presence in mammalian cells, very few studies have investigated its contribution to homeostasis and disease development, thus the role of 3-MST remains largely unexplored. Here, we present a clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR–associated protein-9 (Cas9) induced 3-mst mutant zebrafish line, which will allow the study of 3-MST’s role in several biological processes. The 3-mst zebrafish orthologue was identified using a bioinformatic approach and verified by its ability to produce H2S in the presence of 3-mercaptopyruvate (3-MP). Its expression pattern was analyzed during zebrafish early development, indicating predominantly an expression in the heart and central nervous system. As expected, no detectable levels of 3-Mst protein were observed in homozygous mutant larvae. In line with this, H2S levels were reduced in 3-mst−/− zebrafish. Although the mutants showed no obvious morphological deficiencies, they exhibited increased lethality under oxidative stress conditions. The elevated levels of reactive oxygen species, detected following 3-mst deletion, are likely to drive this phenotype. In line with the increased ROS, we observed accelerated fin regenerative capacity in 3-mst deficient zebrafish. Overall, we provide evidence for the expression of 3-mst in zebrafish, confirm its important role in redox homeostasis and indicate the enzyme’s possible involvement in the regeneration processes. Full article
Open AccessReview
Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement
Biomolecules 2020, 10(2), 316; https://doi.org/10.3390/biom10020316 (registering DOI) - 17 Feb 2020
Viewed by 106
Abstract
: Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to [...] Read more.
: Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to their high specificity and well-known mechanism of action, there has been a growing interest in using them for improving vaccine efficacy. Several studies have shown that ASOs can improve the efficacy of vaccines either by inducing antigen modification such as enhanced expression of immunogenic molecules or by targeting certain components of the host immune system to achieve the desired immune response. However, despite their extended use, some problems such as insufficient stability and low cellular delivery have not been sufficiently resolved to achieve effective and safe ASO-based vaccines. In this review, we analyze the molecular bases and the research that has been conducted to demonstrate the potential use of ASOs in vaccines. Full article
(This article belongs to the Section Biomacromolecules)
Open AccessArticle
Fatty Acid Content and Composition of the Yakutian Horses and Their Main Food Source: Living in Extreme Winter Conditions
Biomolecules 2020, 10(2), 315; https://doi.org/10.3390/biom10020315 (registering DOI) - 17 Feb 2020
Viewed by 100
Abstract
: For the first time, seasonal changes in the content of total lipids (TLs) and phospholipids (PLs) were studied in fodder plants growing in Central Yakutia—a perennial cereal, smooth brome (Bromopsis inermis L.), and an annual cereal, common oat (Avena sativa [...] Read more.
: For the first time, seasonal changes in the content of total lipids (TLs) and phospholipids (PLs) were studied in fodder plants growing in Central Yakutia—a perennial cereal, smooth brome (Bromopsis inermis L.), and an annual cereal, common oat (Avena sativa L.). Both species have concentrated TLs and PLs in autumn under cold hardening. In addition, a significant increase in the content of fatty acids (FAs) of B. inermis was observed during the autumn decrease in temperature. The Yakutian horses, which fed on cereals enriched with nutrients preserved by natural cold (green cryo-fodder), accumulated significant amounts of 18:2n-6 and 18:3n-3, the total content of which in cereals was 75% of the total FA content. We found differences in the distribution of these two FAs in different tissues of the horses. Thus, liver was rich in 18:2n-6, while muscle and adipose tissues accumulated mainly 18:3n-3. Such a distribution may indicate different roles of these FAs in the metabolism of the horses. According to FA content, meat of the Yakutian horses is a valuable dietary product. Full article
(This article belongs to the Special Issue Fatty Acids in Natural Ecosystems and Human Nutrition)
Open AccessArticle
Regulation of Adipsin Expression by Endoplasmic Reticulum Stress in Adipocytes
Biomolecules 2020, 10(2), 314; https://doi.org/10.3390/biom10020314 (registering DOI) - 17 Feb 2020
Viewed by 104
Abstract
Adpsin is an adipokine that stimulates insulin secretion from β-cells and improves glucose tolerance. Its expression has been found to be markedly reduced in obese animals. However, it remains unclear what factors lead to downregulation of adipsin in the context of obesity. Endoplasmic [...] Read more.
Adpsin is an adipokine that stimulates insulin secretion from β-cells and improves glucose tolerance. Its expression has been found to be markedly reduced in obese animals. However, it remains unclear what factors lead to downregulation of adipsin in the context of obesity. Endoplasmic reticulum (ER) stress response is activated in various tissues under obesity-related conditions and can induce transcriptional reprogramming. Therefore, we aimed to investigate the relationship between adipsin expression and ER stress in adipose tissues during obesity. We observed that obese mice exhibited decreased levels of adipsin in adipose tissues and serum and increased ER stress markers in adipose tissues compared to lean mice. We also found that ER stress suppressed adipsin expression via adipocytes-intrinsic mechanisms. Moreover, the ER stress-mediated downregulation of adipsin was at least partially attributed to decreased expression of peroxisome proliferator-activated receptor γ (PPARγ), a key transcription factor in the regulation of adipocyte function. Finally, treatment with chemical chaperones recovered the ER stress-mediated downregulation of adipsin and PPARγ in vivo and in vitro. Our findings suggest that activated ER stress in adipose tissues is an important cause of the suppression of adipsin expression in the context of obesity. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessReview
Brain Cytoplasmic RNAs in Neurons: From Biosynthesis to Function
Biomolecules 2020, 10(2), 313; https://doi.org/10.3390/biom10020313 (registering DOI) - 17 Feb 2020
Viewed by 101
Abstract
Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides [...] Read more.
Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides an important basis for understanding molecular principles of brain function. This approach will have wide use in understanding the pathogenesis of brain diseases and in the development of therapeutic agents in the future. Brain cytoplasmic RNAs (BC RNAs) are a leading paradigm for research on neuronal ncRNAs. Since the first confirmation of brain-specific expression of BC RNAs in 1982, their investigation has been an area of active research. In this review, we summarize key studies on the characteristics and functions of BC RNAs in neurons. Full article
(This article belongs to the Special Issue RNA Trafficking and Local Translation in Neuronal Health and Disease)
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Open AccessReview
The Role of Retinoic Acid in Establishing the Early Limb Bud
Biomolecules 2020, 10(2), 312; https://doi.org/10.3390/biom10020312 (registering DOI) - 17 Feb 2020
Viewed by 95
Abstract
Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the [...] Read more.
Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the role of RA in establishing the domain of cells that will go on to form the limb itself. Although there is some consensus on the role of RA during the earliest stages of limb formation, some controversy remains on the mechanism of RA action and the requirement for RA signaling in forming the hindlimb buds. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
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Open AccessArticle
Integrative Transcriptomic and Metabolic Analyses Provide Insights into the Role of Trichomes in Tea Plant (Camellia Sinensis)
Biomolecules 2020, 10(2), 311; https://doi.org/10.3390/biom10020311 (registering DOI) - 16 Feb 2020
Viewed by 184
Abstract
Trichomes, which develop from epidermal cells, are regarded as one of the key features that are involved in the evaluation of tea quality and tea germplasm resources. The metabolites from trichomes have been well characterized in tea products. However, little is known regarding [...] Read more.
Trichomes, which develop from epidermal cells, are regarded as one of the key features that are involved in the evaluation of tea quality and tea germplasm resources. The metabolites from trichomes have been well characterized in tea products. However, little is known regarding the metabolites in fresh tea trichomes and the molecular differences in trichomes and tea leaves per se. In this study, we developed a method to collect trichomes from tea plant tender shoots, and their main secondary metabolites, including catechins, caffeine, amino acids, and aroma compounds, were determined. We found that the majority of these compounds were significantly less abundant in trichomes than in tea leaves. RNA-Seq was used to investigate the differences in the molecular regulatory mechanism between trichomes and leaves to gain further insight into the differences in trichomes and tea leaves. In total, 52.96 Gb of clean data were generated, and 6560 differentially expressed genes (DEGs), including 4471 upregulated and 2089 downregulated genes, were identified in the trichomes vs. leaves comparison. Notably, the structural genes of the major metabolite biosynthesis pathways, transcription factors, and other key DEGs were identified and comparatively analyzed between trichomes and leaves, while trichome-specific genes were also identified. Our results provide new insights into the differences between tea trichomes and leaves at the metabolic and transcriptomic levels, and open up new doors to further recognize and re-evaluate the role of trichomes in tea quality formation and tea plant growth and development. Full article
(This article belongs to the Section Molecular Biology)
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Open AccessArticle
Production, Characterization, and Bioactivity of Fish Protein Hydrolysates from Aquaculture Turbot (Scophthalmus maximus) Wastes
Biomolecules 2020, 10(2), 310; https://doi.org/10.3390/biom10020310 (registering DOI) - 15 Feb 2020
Viewed by 229
Abstract
The valorization of wastes generated in the processing of farmed fish is currently an issue of extreme relevance for the industry, aiming to accomplish the objectives of circular bioeconomy. In the present report, turbot (Scophthalmus maximus) by-products were subjected to Alcalase [...] Read more.
The valorization of wastes generated in the processing of farmed fish is currently an issue of extreme relevance for the industry, aiming to accomplish the objectives of circular bioeconomy. In the present report, turbot (Scophthalmus maximus) by-products were subjected to Alcalase hydrolysis under the optimal conditions initially defined by response surface methodology. All the fish protein hydrolysates (FPHs) showed a high yield of digestion (>83%), very remarkable degrees of hydrolysis (30–37%), high content of soluble protein (>62 g/L), an excellent profile of amino acids, and almost total in vitro digestibility (higher than 92%). Antioxidant and antihypertensive activities were analyzed in all cases, viscera hydrolysates being the most active. The range of average molecular weights (Mw) of turbot hydrolysates varied from 1200 to 1669 Da, and peptide size distribution showed that the hydrolysate of viscera had the highest content of peptides above 1000 Da and below 200 Da. Full article
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Open AccessArticle
Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization
Biomolecules 2020, 10(2), 309; https://doi.org/10.3390/biom10020309 (registering DOI) - 15 Feb 2020
Viewed by 200
Abstract
Appending a lipophylic alkyl chain by ester bond to fluorescein has been previously shown to convert this popular dye into an effective protonophoric uncoupler of oxidative phosphorylation in mitochondria, exhibiting neuro- and nephroprotective effects in murine models. In line with this finding, we [...] Read more.
Appending a lipophylic alkyl chain by ester bond to fluorescein has been previously shown to convert this popular dye into an effective protonophoric uncoupler of oxidative phosphorylation in mitochondria, exhibiting neuro- and nephroprotective effects in murine models. In line with this finding, we here report data on the pronounced depolarizing effect of a series of fluorescein decyl esters on bacterial cells. The binding of the fluorescein derivatives to Bacillus subtilis cells was monitored by fluorescence microscopy and fluorescence correlation spectroscopy (FCS). FCS revealed the energy-dependent accumulation of the fluorescein esters with decyl(triphenyl)- and decyl(tri-p-tolyl)phosphonium cations in the bacterial cells. The latter compound proved to be the most potent in suppressing B. subtilis growth. Full article
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