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Volume 10, June

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Life, Volume 10, Issue 7 (July 2020) – 14 articles

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Open AccessArticle
UPLC-MS/MS Phytochemical Analysis of Two Croatian Cistus Species and Their Biological Activity
Life 2020, 10(7), 112; https://doi.org/10.3390/life10070112 - 14 Jul 2020
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Abstract
Aqueous extracts of two Cistus species wild growing in Croatia—Cistus creticus (CC) and Cistus salviifolius (CS)—have been assessed with UPLC-MS/MS, showing 43 different phytochemicals, with flavonol glycosides: myricetin-3-hexoside and myricetin-rhamnoside, predominate ones in CC and myricetin-3-hexoside in CS. Antioxidant potential tested with [...] Read more.
Aqueous extracts of two Cistus species wild growing in Croatia—Cistus creticus (CC) and Cistus salviifolius (CS)—have been assessed with UPLC-MS/MS, showing 43 different phytochemicals, with flavonol glycosides: myricetin-3-hexoside and myricetin-rhamnoside, predominate ones in CC and myricetin-3-hexoside in CS. Antioxidant potential tested with the FRAP method showed no difference between CS and CC aqueous extracts, while higher phenolic content of CC comparing to CS, determined with a Folin–Cicolateu reagent correlated to its higher antioxidant capacity observed by the DPPH method. Both extracts were assessed for antimicrobial activity, using disc-diffusion and broth microdilution assays, targeting the opportunistic pathogens, associated with food poisoning, urinary, respiratory tract, blood stream and wound infections in humans. Antimicrobial assays revealed that fungi were in general more sensitive to both Cistus aqueous extracts, comparing to the bacteria where two extracts showed very similar activity. The most potent activity was observed against A. baumannii for both extracts. The extracts were tested on human lung cancer (A549) cell line using the MTT assay, showing very similar antiproliferative activity. After 72 h treatment with CC and CS aqueous extracts in concentration of 0.5 g/L, the viability of the cells were 37% and 50% respectively, compared to non-treated cells. Full article
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Open AccessArticle
Embelin as Lead Compound for New Neuroserpin Polymerization Inhibitors
Life 2020, 10(7), 111; https://doi.org/10.3390/life10070111 - 11 Jul 2020
Viewed by 192
Abstract
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a severe and lethal neurodegenerative disease. Upon specific point mutations in the SERPINI1gene-coding for the human protein neuroserpin (NS) the resulting pathologic NS variants polymerize and accumulate within the endoplasmic reticulum of neurons in [...] Read more.
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a severe and lethal neurodegenerative disease. Upon specific point mutations in the SERPINI1gene-coding for the human protein neuroserpin (NS) the resulting pathologic NS variants polymerize and accumulate within the endoplasmic reticulum of neurons in the central nervous system. To date, embelin (EMB) is the only known inhibitor of NS polymerization in vitro. This molecule is capable of preventing NS polymerization and dissolving preformed polymers. Here, we show that lowering EMB concentration results in increasing size of NS oligomers in vitro. Moreover, we observe that in cells expressing NS, the polymerization of G392E NS is reduced, but this effect is mediated by an increased proteasomal degradation rather than polymerization impairment. For these reasons we designed a systematic chemical evolution of the EMB scaffold aimed to improve its anti-polymerization properties. The effect of EMB analogs against NS polymerization was assessed in vitro. None of the EMB analogs displayed an anti-polymerization activity better than the one reported for EMB, indicating that the EMB–NS interaction surface is very specific and highly optimized. Thus, our results indicate that EMB is, to date, still the best candidate for developing a treatment against NS polymerization. Full article
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Open AccessArticle
Dynamical Behavior and Conformational Selection Mechanism of the Intrinsically Disordered Sic1 Kinase-Inhibitor Domain
Life 2020, 10(7), 110; https://doi.org/10.3390/life10070110 - 11 Jul 2020
Viewed by 190
Abstract
Intrinsically Disordered Peptides and Proteins (IDPs) in solution can span a broad range of conformations that often are hard to characterize by both experimental and computational methods. However, obtaining a significant representation of the conformational space is important to understand mechanisms underlying protein [...] Read more.
Intrinsically Disordered Peptides and Proteins (IDPs) in solution can span a broad range of conformations that often are hard to characterize by both experimental and computational methods. However, obtaining a significant representation of the conformational space is important to understand mechanisms underlying protein functions such as partner recognition. In this work, we investigated the behavior of the Sic1 Kinase-Inhibitor Domain (KID) in solution by Molecular Dynamics (MD) simulations. Our results point out that application of common descriptors of molecular shape such as Solvent Accessible Surface (SAS) area can lead to misleading outcomes. Instead, more appropriate molecular descriptors can be used to define 3D structures. In particular, we exploited Weighted Holistic Invariant Molecular (WHIM) descriptors to get a coarse-grained but accurate definition of the variegated Sic1 KID conformational ensemble. We found that Sic1 is able to form a variable amount of folded structures even in absence of partners. Among them, there were some conformations very close to the structure that Sic1 is supposed to assume in the binding with its physiological complexes. Therefore, our results support the hypothesis that this protein relies on the conformational selection mechanism to recognize the correct molecular partners. Full article
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Open AccessArticle
Optimization of Molecular Dynamics Simulations of c-MYC1-88—An Intrinsically Disordered System
Life 2020, 10(7), 109; https://doi.org/10.3390/life10070109 - 10 Jul 2020
Viewed by 148
Abstract
Many of the proteins involved in key cellular regulatory events contain extensive intrinsically disordered regions that are not readily amenable to conventional structure/function dissection. The oncoprotein c-MYC plays a key role in controlling cell proliferation and apoptosis and more than 70% of the [...] Read more.
Many of the proteins involved in key cellular regulatory events contain extensive intrinsically disordered regions that are not readily amenable to conventional structure/function dissection. The oncoprotein c-MYC plays a key role in controlling cell proliferation and apoptosis and more than 70% of the primary sequence is disordered. Computational approaches that shed light on the range of secondary and tertiary structural conformations therefore provide the only realistic chance to study such proteins. Here, we describe the results of several tests of force fields and water models employed in molecular dynamics simulations for the N-terminal 88 amino acids of c-MYC. Comparisons of the simulation data with experimental secondary structure assignments obtained by NMR establish a particular implicit solvation approach as highly congruent. The results provide insights into the structural dynamics of c-MYC1-88, which will be useful for guiding future experimental approaches. The protocols for trajectory analysis described here will be applicable for the analysis of a variety of computational simulations of intrinsically disordered proteins. Full article
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Open AccessArticle
Molecular Correlation between Larval, Deutonymph and Adult Stages of the Water Mite Arrenurus (Micruracarus) Novus
Life 2020, 10(7), 108; https://doi.org/10.3390/life10070108 (registering DOI) - 09 Jul 2020
Viewed by 221
Abstract
The systematics of many groups of organisms has been based on the adult stage. Morphological transformations that occur during development from the embryonic to the adult stage make it difficult (or impossible) to identify a juvenile (larval) stage in some species. Hydrachnidia (Acari, [...] Read more.
The systematics of many groups of organisms has been based on the adult stage. Morphological transformations that occur during development from the embryonic to the adult stage make it difficult (or impossible) to identify a juvenile (larval) stage in some species. Hydrachnidia (Acari, Actinotrichida, which inhabit mainly continental waters) are characterized by three main active stages—larval, deutonymph and adult—with intermediate dormant stages. Deutonymphs and adults may be identified through diagnostic morphological characters. Larvae that have not been tracked directly from a gravid female are difficult to identify to the species level. In this work, we compared the morphology of five water mite larvae and obtained the molecular sequences of that found on a pupa of the common mosquito Culex (Culex) pipiens with the sequences of 51 adults diagnosed as Arrenurus species and identified the undescribed larvae as Arrenurus (Micruracarus) novus. Further corroborating this finding, adult A. novus was found thriving in the same mosquito habitat. We established the identity of adult and deutonymph A. novus by morphology and by correlating COI and cytB sequences of the water mites at the larval, deutonymph and adult (both male and female) life stages in a particular case of ‘reverse taxonomy’. In addition, we constructed the Arrenuridae phylogeny based on mitochondrial DNA, which supports the idea that three Arrenurus subgenera are ‘natural’: Arrenurus, Megaluracarus and Micruracarus, and the somewhat arbitrary distinction of the species assigned to the subgenus Truncaturus. Full article
(This article belongs to the Special Issue Molecular Phylogenetics and Mitochondrial Evolution)
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Open AccessArticle
Assessing Viral Abundance and Community Composition in Four Contrasting Regions of the Southern Ocean
Life 2020, 10(7), 107; https://doi.org/10.3390/life10070107 - 05 Jul 2020
Viewed by 368
Abstract
We explored how changes of viral abundance and community composition among four contrasting regions in the Southern Ocean relied on physicochemical and microbiological traits. During January–February 2015, we visited areas north and south of the South Orkney Islands (NSO and SSO) characterized by [...] Read more.
We explored how changes of viral abundance and community composition among four contrasting regions in the Southern Ocean relied on physicochemical and microbiological traits. During January–February 2015, we visited areas north and south of the South Orkney Islands (NSO and SSO) characterized by low temperature and salinity and high inorganic nutrient concentration, north of South Georgia Island (NSG) and west of Anvers Island (WA), which have relatively higher temperatures and lower inorganic nutrient concentrations. Surface viral abundance (VA) was highest in NSG (21.50 ± 10.70 × 106 viruses mL−1) and lowest in SSO (2.96 ± 1.48 × 106 viruses mL−1). VA was positively correlated with temperature, prokaryote abundance and prokaryotic heterotrophic production, chlorophyll a, diatoms, haptophytes, fluorescent organic matter, and isoprene concentration, and was negatively correlated with inorganic nutrients (NO3−, SiO42−, PO43−), and dimethyl sulfide (DMS) concentrations. Viral communities determined by randomly amplified polymorphic DNA–polymerase chain reaction (RAPD-PCR) were grouped according to the sampling location, being more similar within them than among regions. The first two axes of a canonical correspondence analysis, including physicochemical (temperature, salinity, inorganic nutrients—NO3−, SiO42−, and dimethyl sulfoniopropionate -DMSP- and isoprene concentrations) and microbiological (chlorophyll a, haptophytes and diatom, and prokaryote abundance and prokaryotic heterotrophic production) factors accounted for 62.9% of the variance. The first axis, temperature-related, accounted for 33.8%; the second one, salinity-related, accounted for 29.1%. Thus, different environmental situations likely select different hosts for viruses, leading to distinct viral communities. Full article
(This article belongs to the Special Issue Microbial Community Structure and Metabolic Networks in Polar Areas)
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Open AccessReview
Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance
Life 2020, 10(7), 106; https://doi.org/10.3390/life10070106 - 04 Jul 2020
Viewed by 320
Abstract
The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure [...] Read more.
The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs. Moreover, in vitro studies are useful to anticipate potential herbal medicine-drug interactions. In particular, they help to elucidate the cellular target (metabolic or transporter protein) and the mechanism (induction or inhibition) by which a single constituent of the herbal medicine acts. The authors highlight the difficulties in predicting herbal–drug interactions from in vitro data where high concentrations of extracts or their constituents are used and pharmacokinetics are missed. Moreover, the difficulty to compare results from human studies where different kinds of herbal extracts are used is discussed. The herbal medicines discussed are among the best sellers and they are reported in the “Herbal Medicines for Human Use” section of the European Medicinal Agency (EMA). Full article
(This article belongs to the Section Pharmaceutical Sciences)
Open AccessCommunication
Nocturnal Lagophthalmos and Sleep Quality in Patients with Dry Eye Disease
Life 2020, 10(7), 105; https://doi.org/10.3390/life10070105 - 04 Jul 2020
Viewed by 253
Abstract
Nocturnal lagophthalmos (NL) refers to the inability to close the eyelids during sleep, which is known to affect dry eye disease (DED) symptoms and sleep quality. This study aimed to evaluate the prevalence of NL and sleep quality in DED patients. We launched [...] Read more.
Nocturnal lagophthalmos (NL) refers to the inability to close the eyelids during sleep, which is known to affect dry eye disease (DED) symptoms and sleep quality. This study aimed to evaluate the prevalence of NL and sleep quality in DED patients. We launched a survey website to recruit 2000 Japanese. The participants were asked to answer a questionnaire about DED, sleep quality, and happiness. Participants were divided into two groups according to the presence of DED, and responses were compared between the groups. The DED group was comprised of 890 subjects (44 ± 13.8 years, 359 males) and women were predominant (p < 0.001). Sleep duration was significantly shorter (p = 0.008), sleep latency was longer (p < 0.001), and sleep efficacy was worse compared with the non-DED group (p < 0.001). Furthermore, people belonging to the DED group were more frequently working night shifts (p < 0.001). NL was more prevalent in the DED group (p = 0.007). Logistic regression analysis showed that NL correlated with younger age, symptomatic DED, and eye symptoms upon waking. The current study suggested that NL was associated with worsened DED symptoms and poor sleep quality. Preventative eye care for lagophthalmos before and during sleep may be helpful for DED and sleep quality. Full article
(This article belongs to the Section Medical Research)
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Open AccessReview
Endosperm of Angiosperms and Genomic Imprinting
Life 2020, 10(7), 104; https://doi.org/10.3390/life10070104 - 03 Jul 2020
Viewed by 278
Abstract
Modern ideas about the role of epigenetic systems in the regulation of gene expression allow us to understand the mechanisms of vital activities in plants, such as genomic imprinting. It is important that genomic imprinting is known first and foremost for the endosperm, [...] Read more.
Modern ideas about the role of epigenetic systems in the regulation of gene expression allow us to understand the mechanisms of vital activities in plants, such as genomic imprinting. It is important that genomic imprinting is known first and foremost for the endosperm, which not only provides an embryo with necessary nutrients, but also plays a special biological role in the formation of seeds and fruits. Available data on genomic imprinting in the endosperm have been obtained only for the triploid endosperm in model plants, which develops after double fertilization in a Polygonum-type embryo sac, the most common type among angiosperms. Here we provide a brief overview of a wide diversity of embryo sacs and endosperm types and ploidy levels, as well as their distribution in the angiosperm families, positioned according to the Angiosperm Phylogeny Group IV (APG IV) phylogenetic classification. Addition of the new, non-model taxa to study gene imprinting in seed development will extend our knowledge about the epigenetic mechanisms underlying angiosperm fertility. Full article
(This article belongs to the Section Life Sciences)
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Open AccessArticle
Small Cyclic Peptide for Pyrophosphate Dependent Ligation in Prebiotic Environments
Life 2020, 10(7), 103; https://doi.org/10.3390/life10070103 - 02 Jul 2020
Viewed by 315
Abstract
All life on Earth uses one universal biochemistry stemming from one universal common ancestor of all known living organisms. One of the most striking features of this universal biochemistry is its utter dependence on phosphate group transfer between biochemical molecules. Both nucleic acid [...] Read more.
All life on Earth uses one universal biochemistry stemming from one universal common ancestor of all known living organisms. One of the most striking features of this universal biochemistry is its utter dependence on phosphate group transfer between biochemical molecules. Both nucleic acid and peptide biological synthesis relies heavily on phosphate group transfer. Such dependents strongly indicate very early incorporation of phosphate chemistry in the origin of life. Perhaps as early as prebiotic soup stage. We report here on a short cyclic peptide, c(RPDDHR), designed rationally for pyrophosphate interaction, which is able to create a new amide bond dependent on the presence of pyrophosphate. We believe this result to be a first step in the exploration of Phosphate Transfer Catalysts that must have been present and active in prebiotic soup and must have laid down foundations for the universal bioenergetics. Full article
(This article belongs to the Special Issue Phosphorus in the Origin of Life)
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Open AccessArticle
Muscular Strength Imbalances Are not Associated with Skin Temperature Asymmetries in Soccer Players
Life 2020, 10(7), 102; https://doi.org/10.3390/life10070102 - 02 Jul 2020
Viewed by 295
Abstract
Although strength imbalances using isokinetic dynamometer have been examined for injury risk screening in soccer players, it is very expensive and time-consuming, making the evaluation of new methods appealing. The aim of the study was to analyze the agreement between muscular strength imbalances [...] Read more.
Although strength imbalances using isokinetic dynamometer have been examined for injury risk screening in soccer players, it is very expensive and time-consuming, making the evaluation of new methods appealing. The aim of the study was to analyze the agreement between muscular strength imbalances and skin temperature bilateral asymmetries as well as skin temperature differences in the hamstrings and quadriceps. The skin temperature of the anterior and posterior thigh of 59 healthy male soccer athletes was assessed at baseline using infrared thermography for the identification of hamstrings-quadriceps skin temperature differences and thermal asymmetries (>0.5 °C). Subsequently, concentric and eccentric peak torque of the quadriceps and hamstrings were considered in the determination of the ratios, as well as muscular asymmetries (>15%). When considering the torque parameters, 37.3% (n = 22) of the players would be classified as high risk for injuries. The percentage of those presenting skin temperature imbalances superior to 0.5 °C was 52.5% (n = 31). The skin temperature assessment showed sensitivity (22%) and specificity (32.2%) to identify torque asymmetries, demonstrating the inability to identify false negatives (15.3%) and false positives (30.5%) from all soccer athletes. In conclusion, skin temperature differences between hamstrings and quadriceps could be more related to thermoregulatory factors than strength imbalances. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Open AccessReview
Interaction of Oxidative Stress and Misfolded Proteins in the Mechanism of Neurodegeneration
Life 2020, 10(7), 101; https://doi.org/10.3390/life10070101 - 30 Jun 2020
Viewed by 339
Abstract
Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer’s and Parkinson’s disease. Activity and toxicity of these proteins depends [...] Read more.
Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer’s and Parkinson’s disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxidative stress and oligomers may cause neuronal death. Full article
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Open AccessArticle
EQ-5D-3L for Assessing Quality of Life in Older Nursing Home Residents with Cognitive Impairment
Life 2020, 10(7), 100; https://doi.org/10.3390/life10070100 - 30 Jun 2020
Viewed by 254
Abstract
Background: Quality of life (QoL) is recognized as an important patient-reported outcome measure. Assessing QoL in older people with cognitive impairment is a challenge due to discrepancies in the collection of data via proxies versus self-report. This study aimed to assess the psychometric [...] Read more.
Background: Quality of life (QoL) is recognized as an important patient-reported outcome measure. Assessing QoL in older people with cognitive impairment is a challenge due to discrepancies in the collection of data via proxies versus self-report. This study aimed to assess the psychometric properties of the self-reported EQ-5D (including the EQ index and EQ visual analog scale (VAS)) in nursing homes residents with cognitive impairment and to analyze its validity based on scales included in the comprehensive geriatric assessment. Methods: Cross-sectional, multicenter study analyzing the feasibility, acceptability, reliability, and validity of the EQ-5D based on 251 self-administered questionnaires in a sample of nursing home residents with cognitive impairment. Reference scales were those from the comprehensive geriatric assessment, equivalent to the five dimensions of the EuroQol. Results: The EQ index was 0.31 (0.37) and the EQ VAS was 35.96 (29.86), showing adequate acceptability and feasibility. Cronbach’s alpha was 0.723. The EQ index and EQ VAS, as outcome variables for multiple linear regression models including CGA titration scales, showed better validity for the EQ index than the EQ VAS. Conclusions: As a self-administered generic scale, the EQ-5D-3L could be a good tool for QoL assessment in nursing home residents with cognitive impairment. Full article
(This article belongs to the Special Issue Mental Health Issues and Quality of Life in Older Individuals)
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Open AccessArticle
Oral Surgical Management of Bone and Soft Tissues in MRONJ Treatment: A Decisional Tree
Life 2020, 10(7), 99; https://doi.org/10.3390/life10070099 - 29 Jun 2020
Viewed by 285
Abstract
Background: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that [...] Read more.
Background: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that is able to standardize clinical decision making and maximize the success of oral surgical treatment of MRONJ. Methods: Different surgical approaches were categorized taking into consideration two variables (a) hard tissue management (defined as debridement, saucerization or marginal resective surgery of maxillary necrotic bone) and (b) soft tissue management (defined as type of flap design and related modality of wound-healing). Results: For the retrospective cohort study, 103 MRONJ patients were enrolled and a total of 128 surgical procedures were performed. The role of radical-intended surgery using local flaps in MRONJ treatment was investigated, as well as palliative treatments. All stage I–II patients completely healed when a combination of radical necrotic bone surgery associated with a first intention healing of soft tissues was obtained. In stage III, when a patient was not eligible for maxillo-facial surgery, the use of palliative surgical strategies was effective in symptom relief in order to maintain a better quality of life for the duration of the patient’s life. Conclusions: Oral surgery with radical intent associated with a flap design able to ensure first intention healing might represent a valid option for the majority of MRONJ patients. The designed decision tree allows clinicians to assess individual surgical approaches for MRONJ treatment in accordance with patient-centered outcomes and surgical skills. Full article
(This article belongs to the Section Medical Research)
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