bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Gene Elongation in the Evolution of Histidine Biosynthetic Genes
Authors: Del Duca Sara , Chioccioli Sofia , Vassallo Alberto , Castronovo Lara Mitia , Fani Renato
Published: May 2020

Gene elongation is a molecular mechanism consisting of an in-tandem duplication of a gene and divergence and fusion of the two copies, resulting in a gene constituted by two divergent paralogous modules. The aim of this work was to evaluate the importance of gene elongation in the evolution of histidine biosynthetic genes and to propose a possible evolutionary model for some of them. Concerning the genes hisA and hisF, which code for two homologous (β/α)8-barrels, it has been proposed that the two extant genes could be the result of a cascade of gene elongation/domain shuffling events starting from an ancestor gene coding for just one (β/α) module. A gene elongation event has also been proposed for the evolution of hisB and hisD; structural analyses revealed the possibility of an early elongation event, resulting in the repetition of modules. Furthermore, it is quite possible that the gene elongations responsible for the evolution of the four proteins occurred before the earliest phylogenetic divergence. In conclusion, gene elongation events seem to have played a crucial role in the evolution of the histidine biosynthetic pathway, and they may have shaped the structures of many genes during the first steps of their evolution.
Probiotic Potential and Technological Properties of Bacteriocinogenic Lactococcus lactis Subsp. Lactis UTNGt28 from a Native Amazonian Fruit as a Yogurt Starter Culture
Authors: Tenea Gabriela N. , Suárez Jimena
Published: May 2020

A native Lactococcus lactis subsp. lactis UTNGt28 (GenBank accession no: MG675576.1) isolated from Amazonian fruit of the tropical Caimitillo (Chrysophyllum oliviforme) tree and the commercial strain Lactococcus lactis subsp lactis ATCC11454 (LacAT) were targeted ex vitro in whole milk in combination with Streptococcus thermophilus ATCC19258 to obtain a fermented probiotic beverage. Concomitant with cell viability determination during storage (28 days), the pH, titratable acidity, syneresis, protein and fat were evaluated. The results indicated that neither UTNGt28 nor LacAT displayed a high capacity to ferment whole milk and survive during storage; a statistically significant difference (p < 0.05) in cell viability was registered for UTNGt28 compared with LacAT when inoculated alone or in combination with S. thermophilus. A principal component analysis showed a clear difference between the yogurt formulations at day 1 and 28 of storage. The PC 1 explained 46.8% of the total variance (day 28), was loaded in the negative (−) direction with titratable acidity (% lactic acid), while the PC 2 explained 22.5% (day 1) with pH. PC 1 was loaded in the positive (+) direction with pH, cell viability, syneresis, fat and protein. Overall results indicated that UTNGt28 has the technological properties for further development of a new probiotic product.
Multidrug-Resistant Pseudomonas aeruginosa Evokes Differential Inflammatory Responses in Human Microglial and Retinal Pigment Epithelial Cells
Authors: Naik Poonam , Singh Sukhvinder , Vishwakarma Sushma , Kaur Inderjeet , Dave Vivek Pravin , Kumar Ashok , Joseph Joveeta
Published: May 2020

Increasing incidences of multidrug-resistant (MDR) pathogens causing endophthalmitis threaten our ability to treat this condition, and the modulation of inflammatory responses by MDR bacteria is not known. In this study, using human microglia and retinal pigment epithelial (RPE) cells, we compare the inflammatory responses of sensitive (S-PA) and multidrug-resistant (MDR-PA) clinical isolates of Pseudomonas aeruginosa. Infected cells were subjected to qPCR analysis, enzyme-linked immunosorbent assay (ELISA), and immunostaining to assess the expression of inflammatory mediators. Both microglia and RPE cells, challenged with S-PA and MDR-PA, induced a time-dependent expression of inflammatory cytokines. Significant differences were observed in expression levels of Toll-like receptors (TLR) TLR4, TLR5, and TLR9 in microglia cells challenged with MDR-PA vs. S-PA. Similarly, mRNA levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, Interferon (IFN)-γ, and matrix metalloproteinase (MMP)-9 were also higher in MDR-PA-infected cells. At protein levels, upregulation was observed for IL-10 (p = 0.004), IL-8 (p = 0.0006), IL-1β (p = 0.02), and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (p = 0.0006) in cells infected MDR-PA versus S-PA in both microglia and RPE cells; however, the response was delayed in RPE cells. Heatmap and STRING analysis highlighted the existence of a cross-talk between the inflammatory and cytokine-mediated signaling pathways. Our study highlights a differential inflammatory response evoked by MDR vs. sensitive pathogens in retinal cells during endophthalmitis.
Radial Extracorporeal Shock Wave Therapy against Cutibacterium acnes Implant-Associated Infections: An in Vitro Trial
Authors: Tsikopoulos Konstantinos , Drago Lorenzo , Koutras Georgios , Givissis Panagiotis , Vagdatli Eleni , Soukiouroglou Prodromos , Papaioannidou Paraskevi
Published: May 2020

Background: Antibiotic management of low-virulent implant-associated infections induced by Cutibacterium acnes may be compromised by multi-drug resistance development, side effects, and increased cost. Therefore, we sought to assess the effects of shock wave therapy against the above pathogen using an in vitro model of infection. Methods: We used a total of 120 roughened titanium alloy disks, simulating orthopedic biomaterials, to assess the results of radial extracorporeal shock wave therapy (rESWT) against C. acnes (ATCC 11827) biofilms relative to untreated control. In particular, we considered 1.6 to 2.5 Bar with a frequency ranging from 8–11 Hz and 95 to 143 impulses per disk to investigate the antibacterial effect of rESWT against C. acnes planktonic (free-floating) and biofilm forms. Results: Planktonic bacteria load diminished by 54% compared to untreated control after a 1.8-bar setting with a frequency of 8 Hz and 95 impulses was applied (median absorbance (MA) for intervention vs. control groups was 0.9245 (IQR= 0.888 to 0.104) vs. 0.7705 (IQR = 0.712 to 0.864), respectively, p = 0.001). Likewise, a statistically significant reduction in the amount of biofilm relative to untreated control was documented when the above setting was considered (MA for treatment vs biofilm control groups was 0.244 (IQR= 0.215–0.282) and 0.298 (IQR = 0.247–0.307), respectively, p = 0.033). Conclusion: A 50% biofilm eradication was documented following application of low-pressure and low-frequency radial shock waves, so rESWT could be investigated as an adjuvant treatment to antibiotics, but it cannot be recommended as a standalone treatment against device-associated infections induced by C. ances.
Effective Treatment of Acid Mine Drainage with Microbial Fuel Cells: An Emphasis on Typical Energy Substrates
Authors: Ai Chenbing , Yan Zhang , Hou Shanshan , Zheng Xiaoya , Zeng Zichao , Amanze Charles , Dai Zhimin , Chai Liyuan , Qiu Guanzhou , Zeng Weimin
Published: May 2020

Acid mine drainage (AMD), characterized by a high concentration of heavy metals, poses a threat to the ecosystem and human health. Bioelectrochemical system (BES) is a promising technology for the simultaneous treatment of organic wastewater and recovery of metal ions from AMD. Different kinds of organic wastewater usually contain different predominant organic chemicals. However, the effect of different energy substrates on AMD treatment and microbial communities of BES remains largely unknown. Here, results showed that different energy substrates (such as glucose, acetate, ethanol, or lactate) affected the startup, maximum voltage output, power density, coulombic efficiency, and microbial communities of the microbial fuel cell (MFC). Compared with the maximum voltage output (55 mV) obtained by glucose-fed-MFC, much higher maximum voltage output (187 to 212 mV) was achieved by MFCs fed individually with other energy substrates. Acetate-fed-MFC showed the highest power density (195.07 mW/m2), followed by lactate (98.63 mW/m2), ethanol (52.02 mW/m2), and glucose (3.23 mW/m2). Microbial community analysis indicated that the microbial communities of anodic electroactive biofilms changed with different energy substrates. The unclassified_f_Enterobacteriaceae (87.48%) was predominant in glucose-fed-MFC, while Geobacter species only accounted for 0.63%. The genera of Methanobrevibacter (23.70%), Burkholderia-Paraburkholderia (23.47%), and Geobacter (11.90%) were the major genera enriched in the ethanol-fed-MFC. Geobacter was most predominant in MFC enriched by lactate (45.28%) or acetate (49.72%). Results showed that the abundance of exoelectrogens Geobacter species correlated to electricity-generation capacities of electroactive biofilms. Electroactive biofilms enriched with acetate, lactate, or ethanol effectively recovered all Cu2+ ion (349 mg/L) of simulated AMD in a cathodic chamber within 53 h by reduction as Cu0 on the cathode. However, only 34.65% of the total Cu2+ ion was removed in glucose-fed-MFC by precipitation with anions and cations rather than Cu0 on the cathode.
Clerodane Diterpenoids from Callicarpa hypoleucophylla and Their Anti-Inflammatory Activity
Authors: Lin Yu-Chi , Lin Jue-Jun , Chen Shu-Rong , Hwang Tsong-Long , Fang Shu-Yen , Korinek Michal , Chen Ching-Yeu , Lin Yun-Sheng , Wu Tung-Ying , Yen Ming-Hong , Wang Chih-Hsin , Cheng Yuan-Bin
Published: May 2020

Plants of the genus Callicarpa are known to possess several medicinal effects. The constituents of the Taiwan endemic plant Callicarpa hypoleucophylla have never been studied. Therefore, C. hypoleucophylla was selected for our phytochemical investigation. Two new clerodane-type diterpenoids, named callihypolins A (1) and B (2), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant C. hypoleucophylla and then characterized. The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds 1–9 based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds 2–4 showed anti-inflammatory activity (9.52−32.48% inhibition at the concentration 10 μm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus Callicarpa but also highlight the possibility of developing anti-inflammatory agents from Callicarpa endemic species.
Surfactantless Emulsions Containing Eugenol for Imidacloprid Solubilization: Physicochemical Characterization and Toxicity against Insecticide-Resistant Cimex lectularius
Authors: Cáceres Mariano , Guzmán Eduardo , Alvarez-Costa Agustín , Ortega Francisco , G. Rubio Ramón , Coviella Carlos , Santo Orihuela Pablo L. , Vassena Claudia V. , Lucia Alejandro
Published: May 2020

Synthetic insecticides have been used for a long time as one of the most effective tools for insect pest control. However, the re-emergence of insect pests and their fast development of resistance, as has occurred for pyrethroid-resistant bed bugs Cimex lectularius L., make it necessary to develop new and safe strategies for effective pest control. This has fostered the research on new eco-sustainable formulations based on essential oils, which allows reducing the impact associated with the intensive use of synthetic insecticides on the environment and their effects on human health. This research explores the stability of water/eugenol/ethanol surfactantless emulsions loaded with imidacloprid (0.003 wt%), and their toxicity against a resistant bed bug strain. The results have shown that these emulsions enable the solubilization of a poorly water-soluble drug, such as the imidacloprid, without any significant modification of their stability. Furthermore, the application of the obtained formulations against the pyrethroid-resistant bed bug results in mortality in the 50–85% range upon topical and spray applications, with the increase of the eugenol content enhancing the effectiveness of the formulations. It may be expected that the ternary water/eugenol/ethanol mixtures could be further developed in the preparation of ready to use formulations, enabling the dispersion of insecticides for pest control.
Modulating the Properties of Fe(III) Macrocyclic MRI Contrast Agents by Appending Sulfonate or Hydroxyl Groups
Authors: Asik Didar , Smolinski Rachel , Abozeid Samira M. , Mitchell Travis B. , Turowski Steven G. , Spernyak Joseph A. , Morrow Janet R.
Published: May 2020

Complexes of Fe(III) that contain a triazacyclononane (TACN) macrocycle, two pendant hydroxyl groups, and a third ancillary pendant show promise as MRI contrast agents. The ancillary group plays an important role in tuning the solution relaxivity of the Fe(III) complex and leads to large changes in MRI contrast enhancement in mice. Two new Fe(III) complexes, one with a third coordinating hydroxypropyl pendant, Fe(L2), and one with an anionic non-coordinating sulfonate group, Fe(L1)(OH2), are compared. Both complexes have a deprotonated hydroxyl group at neutral pH and electrode potentials representative of a stabilized trivalent iron center. The r1 relaxivity of the Fe(L1)(OH2) complex is double that of the saturated complex, Fe(L2), at 4.7 T, 37 °C in buffered solutions. However, variable-temperature 17O-NMR experiments show that the inner-sphere water of Fe(L1)(OH2) does not exchange rapidly with bulk water under these conditions. The pendant sulfonate group in Fe(L1)(OH2) confers high solubility to the complex in comparison to Fe(L2) or previously studied analogues with benzyl groups. Dynamic MRI studies of the two complexes showed major differences in their pharmacokinetics clearance rates compared to an analogue containing a benzyl ancillary group. Rapid blood clearance and poor binding to serum albumin identify Fe(L1)(OH2) for development as an extracellular fluid contrast agent.
Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells
Authors: Yammine Aline , Nury Thomas , Vejux Anne , Latruffe Norbert , Vervandier-Fasseur Dominique , Samadi Mohammad , Greige-Gerges Hélène , Auezova Lizette , Lizard Gérard
Published: May 2020

The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidation. So, preventing the neuronal toxicity of 7KC is an important issue to avoid brain damage. As there are numerous data in favor of the prevention of neurodegeneration by the Mediterranean diet, this study aimed to evaluate the potential of a series of polyphenols (resveratrol, RSV; quercetin, QCT; and apigenin, API) as well as ω3 and ω9 unsaturated fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA, and oleic acid, OA) widely present in this diet, to prevent 7KC (50 µM)-induced dysfunction of N2a neuronal cells. When polyphenols and fatty acids were used at non-toxic concentrations (polyphenols: ≤6.25 µM; fatty acids: ≤25 µM) as defined by the fluorescein diacetate assay, they greatly reduce 7KC-induced toxicity. The cytoprotective effects observed with polyphenols and fatty acids were comparable to those of α-tocopherol (400 µM) used as a reference. These polyphenols and fatty acids attenuate the overproduction of reactive oxygen species and the 7KC-induced drop in mitochondrial transmembrane potential (ΔΨm) measured by flow cytometry after dihydroethidium and DiOC6(3) staining, respectively. Moreover, the studied polyphenols and fatty acids reduced plasma membrane permeability considered as a criterion for cell death measured by flow cytometry after propidium iodide staining. Our data show that polyphenols (RSV, QCT and API) as well as ω3 and ω9 unsaturated fatty acids (ALA, EPA, DHA and OA) are potent cytoprotective agents against 7KC-induced neurotoxicity in N2a cells. Their cytoprotective effects could partly explain the benefits of the Mediterranean diet on human health, particularly in the prevention of neurodegenerative diseases.
ZeOxaNMulti Trial: A Randomized, Double-Blinded, Placebo-Controlled Trial of Oral PMA-Zeolite to Prevent Chemotherapy-Induced Side Effects, in Particular, Peripheral Neuropathy
Authors: Vitale Maria Giuseppa , Barbato Carmela , Crispo Anna , Habetswallner Francesco , De Martino Bernardo Maria , Riccardi Ferdinando , Maione Angela , Eisenwagen Sandra , Vitale Giovanna , Cartenì Giacomo
Published: May 2020

Chemotherapy-induced peripheral neuropathy (CIPN) is the most frequently reported adverse effect of oxaliplatin. In this study, we set out to evaluate the role of the panaceo-micro-activation (PMA) zeolite in the reduction of the incidence of CIPN and hematological and liver toxicity. The possible impact of the PMA-zeolite as an adjuvant therapeutic agent is based on its detoxification properties toward agents promoting the development of neuropathy (e.g., ammonium—recognized as a neurotoxic agent produced by tumors), as well as its positive impact on immunity and oxidative stress through its effects in the gastrointestinal tract. From April 2015 to October 2018, a total of 120 patients (pts) diagnosed with predominantly colorectal cancer requiring oxaliplatin-based chemotherapy were randomized to receive either the PMA-zeolite (Multizeo Med) or placebo while undergoing oxaliplatin-based chemotherapy. A nerve-conduction study (NCS) was planned at the baseline, after three and six months of chemotherapy, to evaluate CIPN. Furthermore, the evaluation of hematological and liver toxicity was performed during every cycle of chemotherapy. 70.6% and 64.3% of patients developed CIPN in the placebo and the PMA-zeolite group, respectively. Patients treated with the PMA-zeolite were able to undergo more cycles of chemotherapy (p = 0.03), which also indicates a significant improvement in tolerance to the therapy. The group treated with the PMA-zeolite showed a lower CIPN (although not statistically significant within the whole group of subjects) compared to patients receiving placebo. This advantage was, however, statistically significant in men (p = 0.047). In addition, supplementation with the PMA-zeolite resulted in a lower incidence of severe-grade hematological toxicity (trend toward statistical significance of p = 0.09 was observed). Cancer patients may benefit from the therapy with the appropriate certified zeolite-products (e.g., the PMA-zeolite) for human use in CIPN. The lower CIPN (statistically significant results in the male subgroup) was accompanied by a trend of lower incidence of severe-grade hematological toxicity. Furthermore, these benefits led to a better tolerance toward chemotherapy (increase in cycles) and allow an improved compliance with the oncological treatment protocol.
Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review
Authors: Garcia Patricia Mae , Moore Jeff , Kahan David , Hong Mee Young
Published: May 2020

Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as “vitamin D,” “colitis,” “inflammatory bowel disease,” “inflammation,” “apoptosis,” “cell proliferation,” and “gut bacteria”. Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis.
Anti-Cancer Potential of Oxialis obtriangulata in Pancreatic Cancer Cell through Regulation of the ERK/Src/STAT3-Mediated Pathway
Authors: An Eun-Jin , Kim Yumi , Lee Seung-Hyeon , Ko Hyun Min , Chung Won-Seok , Jang Hyeung-Jin
Published: May 2020

As a plant medicine, Oxalidaceae has been used to treat various diseases in Korea. However, there is little data on the anti-cancer efficacy of Oxalidaceae, particularly O. obtriangulata. This study aimed to investigate the anti-cancer effect of O. obtriangulata methanol extract (OOE) and its regulatory actions on pancreatic carcinoma. OOE showed anti-proliferative effects and induced cell death in the colony formation and cell viability assays, respectively. The Fluorescence-activated cell sorting (FACS) data confirmed that OOE significantly induced cell cycle accumulation at the G2/M phase and apoptotic effects. Additionally, OOE inhibited the activated ERK (extracellular-signal-regulated kinase)/Src (Proto-oncogene tyrosine-protein kinase Src)/STAT3 (signal transducers and activators of transcription 3) pathways including nuclear translocation of STAT3. Furthermore, suppression of Ki67, PARP(Poly ADP-ribose polymerase), caspase-3, P27(Cyclin-dependent kinase inhibitor 1B), and c-Myc as well as the STAT3 target genes CDK(cyclin-dependent kinase)1, CDK2, Cyclin B1, VEGF-1(vascular endothelial growth factor-1), MMP-9(Matrix metallopeptidase 9), and Survivin by OOE was observed in BxPC3. We speculate that these molecular actions might support an anti-cancer effect of OOE. In this study, we demonstrated that OOE may be a promising anti-cancer material and may serve as a natural therapy and alternative remedy for pancreatic cancer treatment.
Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3
Authors: Qi Xin , Li Meng , Zhang Xiao-min , Dai Xiu-fen , Cui Jian , Li De-hai , Gu Qian-qun , Lv Zhi-hua , Li Jing
Published: May 2020

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes to cancer progression through multiple processes of cancer development, which makes it an attractive target for cancer therapy. The IL-6/STAT3 pathway is associated with an advanced stage in colorectal cancer patients. In this study, we identified trichothecin (TCN) as a novel STAT3 inhibitor. TCN was found to bind to the SH2 domain of STAT3 and inhibit STAT3 activation and dimerization, thereby blocking STAT3 nuclear translocation and transcriptional activity. TCN did not affect phosphorylation levels of STAT1. TCN significantly inhibited cell growth, arrested cell cycle at the G0/G1 phase, and induced apoptosis in HCT 116 cells. In addition, the capacities of colony formation, migration, and invasion of HCT 116 cells were impaired upon exposure to TCN with or without IL-6 stimulation. In addition, TCN treatment abolished the tube formation of HUVEC cells in vitro. Taken together, these results highlight that TCN inhibits various cancer-related features in colorectal cancer development in vitro by targeting STAT3, indicating that TCN is a promising STAT3 inhibitor that deserves further exploration in the future.
Synthesis of Chitosan Beads Incorporating Graphene Oxide/Titanium Dioxide Nanoparticles for In Vivo Studies
Authors: Grande Tovar Carlos David , Castro Jorge Iván , Valencia Carlos Humberto , Zapata Paula A. , Solano Moisés A. , Florez López Edwin , Chaur Manuel N. , Valencia Zapata Mayra Eliana , Mina Hernandez José Herminsul
Published: May 2020

Scaffold development for cell regeneration has increased in recent years due to the high demand for more efficient and biocompatible materials. Nanomaterials have become a critical alternative for mechanical, thermal, and antimicrobial property reinforcement in several biopolymers. In this work, four different chitosan (CS) bead formulations crosslinked with glutaraldehyde (GLA), including titanium dioxide nanoparticles (TiO2), and graphene oxide (GO) nanosheets, were prepared with potential biomedical applications in mind. The characterization of by FTIR spectroscopy, X-ray photoelectron spectroscopy (XRD), thermogravimetric analysis (TGA), energy-dispersive spectroscopy (EDS) and scanning electron microscopy (SEM), demonstrated an efficient preparation of nanocomposites, with nanoparticles well-dispersed in the polymer matrix. In vivo, subdermal implantation of the beads in Wistar rat′s tissue for 90 days showed a proper and complete healing process without any allergenic response to any of the formulations. Masson′s trichrome staining of the histological implanted tissues demonstrated the presence of a group of macrophage/histiocyte compatible cells, which indicates a high degree of biocompatibility of the beads. The materials were very stable under body conditions as the morphometry studies showed, but with low resorption percentages. These high stability beads could be used as biocompatible, resistant materials for long-term applications. The results presented in this study show the enormous potential of these chitosan nanocomposites in cell regeneration and biomedical applications.
Development of Novel Analogs of the Monocarboxylate Transporter Ligand FACH and Biological Validation of One Potential Radiotracer for Positron Emission Tomography (PET) Imaging
Authors: Sadeghzadeh Masoud , Wenzel Barbara , Gündel Daniel , Deuther-Conrad Winnie , Toussaint Magali , Moldovan Rareş-Petru , Fischer Steffen , Ludwig Friedrich-Alexander , Teodoro Rodrigo , Jonnalagadda Shirisha , Jonnalagadda Sravan K. , Schüürmann Gerrit , Mereddy Venkatram R. , Drewes Lester R. , Brust Peter
Published: May 2020

Monocarboxylate transporters 1-4 (MCT1-4) are involved in several metabolism-related diseases, especially cancer, providing the chance to be considered as relevant targets for diagnosis and therapy. [18F]FACH was recently developed and showed very promising preclinical results as a potential positron emission tomography (PET) radiotracer for imaging of MCTs. Given that [18F]FACH did not show high blood-brain barrier permeability, the current work is aimed to investigate whether more lipophilic analogs of FACH could improve brain uptake for imaging of gliomas, while retaining binding to MCTs. The 2-fluoropyridinyl-substituted analogs 1 and 2 were synthesized and their MCT1 inhibition was estimated by [14C]lactate uptake assay on rat brain endothelial-4 (RBE4) cells. While compounds 1 and 2 showed lower MCT1 inhibitory potencies than FACH (IC50 = 11 nM) by factors of 11 and 25, respectively, 1 (IC50 = 118 nM) could still be a suitable PET candidate. Therefore, 1 was selected for radiosynthesis of [18F]1 and subsequent biological evaluation for imaging of the MCT expression in mouse brain. Regarding lipophilicity, the experimental log D7.4 result for [18F]1 agrees pretty well with its predicted value. In vivo and in vitro studies revealed high uptake of the new radiotracer in kidney and other peripheral MCT-expressing organs together with significant reduction by using specific MCT1 inhibitor α-cyano-4-hydroxycinnamic acid. Despite a higher lipophilicity of [18F]1 compared to [18F]FACH, the in vivo brain uptake of [18F]1 was in a similar range, which is reflected by calculated BBB permeabilities as well through similar transport rates by MCTs on RBE4 cells. Further investigation is needed to clarify the MCT-mediated transport mechanism of these radiotracers in brain.
HILIC-ESI-FTMS with All Ion Fragmentation (AIF) Scans as a Tool for Fast Lipidome Investigations
Authors: Ventura Giovanni , Bianco Mariachiara , Calvano Cosima Damiana , Losito Ilario , Cataldi Tommaso R. I.
Published: May 2020

Lipidomics suffers from the lack of fast and reproducible tools to obtain both structural information on intact phospholipids (PL) and fatty acyl chain composition. Hydrophilic interaction liquid chromatography with electrospray ionization coupled to an orbital-trap Fourier-transform analyzer operating using all ion fragmentation mode (HILIC-ESI-FTMS-AIF MS) is seemingly a valuable resource in this respect. Here, accurate m/z values, HILIC retention times and AIF MS scan data were combined for PL assignment in standard mixtures or real lipid extracts. AIF scans in both positive and negative ESI mode, achieved using collisional induced dissociation for fragmentation, were applied to identify both the head-group of each PL class and the fatty acyl chains, respectively. An advantage of the AIF approach was the concurrent collection of tandem MS-like data, enabling the identification of linked fatty acyl chains of precursor phospholipids through the corresponding carboxylate anions. To illustrate the ability of AIF in the field of lipidomics, two different types of real samples, i.e., the lipid extracts obtained from human plasma and dermal fibroblasts, were examined. Using AIF scans, a total of 253 intact lipid species and 18 fatty acids across 4 lipid classes were recognized in plasma samples, while FA C20:3 was confirmed as the fatty acyl chain belonging to phosphatidylinositol, PI 38:3, which was found to be down-regulated in fibroblast samples of Parkinson’s disease patients.
Enhancement of Antibacterial Performance of Silver Nanowire Transparent Film by Post-Heat Treatment
Authors: Kim Ji-Hyeon , Ma Junfei , Jo Sungjin , Lee Seunghun , Kim Chang Su
Published: May 2020

Silver nanomaterials (AgNMs) have been applied as antibacterial agents to combat bacterial infections that can cause disease and death. The antibacterial activity of AgNMs can be improved by increasing the specific surface area, so significant efforts have been devoted to developing various bottom-up synthesis methods to control the size and shape of the particles. Herein, we report on a facile heat-treatment method that can improve the antibacterial activity of transparent silver nanowire (AgNW) films in a size-controllable, top-down manner. AgNW films were fabricated via spin-coating and were then heated at different temperatures (230 and 280 °C) for 30 min. The morphology and the degree of oxidation of the as-fabricated AgNW film were remarkably sensitive to the heat-treatment temperature, while the transparency was insensitive. As the heat-treatment temperature increased, the AgNWs spontaneously broke into more discrete wires and droplets, and oxidation proceeded faster. The increase in the heat-treatment temperature further increased the antibacterial activity of the AgNW film, and the heat treatment at 280 °C improved the antibacterial activity from 31.7% to 94.7% for Staphylococcus aureus, and from 57.0% to 98.7% for Escherichia coli. Following commonly accepted antibacterial mechanisms of AgNMs, we present a correlation between the antibacterial activity and surface observations of the AgNW film.
Quasi-3D Plasmonic Nanowell Array for Molecular Enrichment and SERS-Based Detection
Authors: Kim Sunho , Mun Chaewon , Choi Dae-Geun , Jung Ho Sang , Kim Dong-Ho , Kim Shin-Hyun , Park Sung-Gyu
Published: May 2020

We report on a quasi-three-dimensional (3D) plasmonic nanowell array with high structural uniformity for molecular detection. The quasi-3D plasmonic nanowell array was composed of periodic hexagonal Au nanowells whose surface is densely covered with gold nanoparticles (Au NPs), separated by an ultrathin dielectric interlayer. The uniform array of the Au nanowells was fabricated by nanoimprint lithography and deposition of Au thin film. A self-assembled monolayer (SAM) of perfluorodecanethiol (PFDT) was coated on the Au surface, on which Au was further deposited. Interestingly, the PFDT-coated Au nanowells were fully covered with Au NPs with an ultra-high density of 375 μm−2 rather than a smooth film due to the anti-wetting property of the low-energy surface. The plasmonic nanogaps formed among the high-density Au NPs led to a strong near-field enhancement via coupled localized surface plasmon resonance and produced a uniform surface-enhanced Raman spectroscopy (SERS) response with a small relative standard deviation of 5.3%. Importantly, the highly uniform nanostructure, featured by the nanoimprint lithography and 3D growth of densely-packed Au NPs, minimizes the spatial variation of Raman intensity, potentially providing quantitative analysis. Moreover, analyte molecules were highly concentrated and selectively deposited in nanowells when a water droplet containing the analyte was evaporated on the plasmonic substrate. The analyte formed a relatively thick overcoat in the nanowells near the triple line due to the coffee-ring effects. Combining 3D plasmonic nanowell substrates with molecular enrichments, highly sensitive detection of lactic acid was demonstrated. Given its combination of high sensitivity and signal uniformity, the quasi-3D plasmonic nanowell substrate is expected to provide a superior molecular detection platform for biosensing applications.
Direct Preparation of Cellulose Nanofibers from Bamboo by Nitric Acid and Hydrogen Peroxide Enables Fibrillation via a Cooperative Mechanism
Authors: Wang Jinlong , Li Xusheng , Song Jianxiao , Wu Kunze , Xue Yichun , Wu Yiting , Wang Shuangfei
Published: May 2020

Separating the fibers, deconstructing both the interlamellar structures and the intermicrofibrils structures in the cell wall, and cleaving the amorphous regions of cellulose (all reached in one bath chemical-assisted treatment), then extracting cellulose nanofibers (CNFs) from biomass, is both challenging and imperative. A simple, cost-effective and green strategy for extracting CNFs from bamboo using nitric acid and hydrogen peroxide (NCHP), to enable fibrillation via a cooperative mechanism, is demonstrated herein. NCHP-CNFs 13.1 ± 2.0 nm wide, with a high aspect ratio, 74% crystallinity, excellent UV resistance and high thermal stability, were successfully extracted by treatment in HNO3 aqueous solution, at a concentration of 3.2 mol/L, and treatment with 60.00 mmol/g H2O2 at 50 °C for 48 h. The yields of NCHP-CNFs reached 73% and 99% based on biomass and cellulose, respectively, due to the high delignification selectivity of OH+ and the mild aqueous conditions during the NCHP treatment. These NCHP-CNFs with excellent UV resistance can potentially be applied in the field of UV-resistant coatings, to replace organic and inorganic materials.
Mindful Eating and Active Living: Development and Implementation of a Multidisciplinary Pediatric Weight Management Intervention
Authors: Burton E. Thomaseo , Smith Webb A.
Published: May 2020

Pediatric overweight and obesity are significant individual and public health issues that require an innovative approach. While evidence suggests that intensive family-based behavioral lifestyle modification can improve weight status, practical and logistical realities limit the ability of primary healthcare providers to intervene effectively. MEALs (Multidisciplinary Engagement and Learning/Mindful Eating and Active Living) is a family-based mindfulness intervention developed to address pediatric overweight and obesity, while improving healthy lifestyle behaviors through cooking classes. The incorporation of mindfulness, a psychological strategy associated with increased awareness of internal experiences, allows for a focus on the importance of healthy eating along with safe and efficacious kitchen practices. The Template for Intervention Description and Replication (TIDieR) checklist and guide is used to describe the intervention with the intention of providing necessary details to implement the intervention in clinical practice or replicate the intervention for further study. Lessons learned from pilot iterations of the intervention are provided.
Defatted Tenebrio molitor Larva Fermentation Extract Modifies Steatosis, Inflammation and Intestinal Microflora in Chronic Alcohol-Fed Rats
Authors: Choi Ra-Yeong , Ham Ju Ri , Ryu Hyo-Seon , Lee Sang Suk , Miguel Michelle A. , Paik Man-Jeong , Ji Moongi , Park Kyung-Wuk , Kang Kyung-Yun , Lee Hae-In , Lee Mi-Kyung
Published: May 2020

This study examined the effects of defatted mealworm fermentation extract (MWF) on alcoholic liver injury in rats. The rats were fed either a Lieber-DeCarli control (Con) or alcohol liquid diet (EtOH). The alcohol-fed rats were administered MWF (50, 100, or 200 mg/kg/day) and silymarin (200 mg/kg/day) orally for eight weeks. MWF prevented alcohol-induced hepatocellular damage by decreasing their serum aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase levels significantly compared to the EtOH group. MWF effectively reduced the relative hepatic weight, lipid contents, and fat deposition, along with the down-regulation of transcriptional factors and genes involved in lipogenesis compared to the EtOH group. It also enhanced the antioxidant defense system by elevating the glutathione level and glutathione reductase activity. MWF attenuated the alcohol-induced inflammatory response by down-regulating hepatic inflammation-associated proteins expression, such as phosphorylated-inhibitor of nuclear factor-kappa B-alpha and tumor necrosis factor-alpha, in chronic alcohol-fed rats. Furthermore, sequencing analysis in the colonic microbiota showed that MWF tended to increase Lactobacillus johnsonii reduced by chronic alcohol consumption. These findings suggest that MWF can attenuate alcoholic liver injury by regulating the lipogenic and inflammatory pathway and antioxidant defense system, as well as by partially altering the microbial composition.
Calcium Bioavailability of Opuntia ficus-indica Cladodes in an Ovariectomized Rat Model of Postmenopausal Bone Loss
Authors: Quintero-García Michelle , Gutiérrez-Cortez Elsa , Rojas-Molina Alejandra , Mendoza-Ávila Monsserrat , Del Real Alicia , Rubio Efraín , Jiménez-Mendoza Daniel , Rojas-Molina Isela
Published: May 2020

Osteoporosis is a disease of the skeletal system characterized by low bone mass and bone weakening, which increase the risk of fracture. This disease is associated with menopause because hypoestrogenism induces the maturation and activation of osteoclasts. In addition, a low dietary intake of calcium leads to low bone mineral density and postmenopausal osteoporosis. The objectives of this work were to determine calcium bioavailability of Opuntia ficus-indica cladodes at a late maturity stage and to assess its contribution in improving bone health in an ovariectomized rat model. Two-month-old Wistar female rats (n = 35) were used and distributed in seven experimental groups: (i) control group (Crtl), (ii) sham group (SH), (iii) ovariectomized group (OVX), (iv) ovariectomized group supplemented with calcium citrate (CCa), (v) ovariectomized group supplemented with O. ficus-indica powder (NI), (vi) ovariectomized group supplemented with soluble fiber from O. ficus-indica (FS) and (vii) ovariectomized group supplemented with insoluble fiber from O. ficus-indica (FI). Our results showed that calcium in the soluble fiber of O. ficus-indica is bioavailable and contributes to improve the physical, densitometric, biomechanical and microstructural properties of bones in ovariectomized rats. These findings indicated that O. ficus-indica cladodes at a late maturity stage represent a good source of bioavailable calcium and consumption of these cladodes might be beneficial for the prevention of osteoporosis and other bone diseases.
The Neuroendocrine Neoplasms of the Digestive Tract: Diagnosis, Treatment and Nutrition
Authors: Pobłocki Jakub , Jasińska Anna , Syrenicz Anhelli , Andrysiak-Mamos Elżbieta , Szczuko Małgorzata
Published: May 2020

Nuroendocrine neoplasms (NENs) are a group of rare neoplasms originating from dispersed neuroendocrine cells, mainly of the digestive and respiratory tract, showing characteristic histology and immunoprofile contributing to classification of NENs. Some NENs have the ability to produce biogenic amines and peptide hormones, which may be associated with clinical syndromes like, e.g., the carcinoid syndrome caused by unmetabolized overproduced serotonin, hypoglycemic syndrome in case of insulinoma, or Zollinger-Ellison syndrome accompanying gastrinoma. Diagnostics for these include ultrasound with endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography/computed tomography (PET/CT). Different nuclear medicine procedures can also be used, like somatostatin analogues scintigraphy (SRS) and 68Ga-Dota-Peptide PET/CT, as well as biochemical methods to determine the level of general neuroendocrine markers, such as chromogranin A (CgA), 5-hydroxyindolacetic acid (5-HIAA), synaptopfysin and cell type-specific peptide hormones, and neurotransmitters like gastrin, insulin, serotonin, and histamine. NENs influence the whole organism by modulating metabolism. The treatment options for neuroendocrine neoplasms include surgery, somatostatin analogue therapy, radionuclide therapy, chemotherapy, molecular targeted therapies, alpha-interferon therapy, and inhibitors of serotonin production. In the case of hypersensitivity to biogenic amines, a diet that limits the main sources of amines should be used. The symptoms are usually connected with histamine, tyramine and putrescine. Exogenic sources of histamine are products that take a long time to mature and ferment. Patients with a genetic insufficiency of the diamine oxidase enzyme (DAO), and those that take medicine belonging to the group of monoamine oxidases (MAO), are particularly susceptible to the negative effects of amines. Diet plays an important role in the initiation, promotion, and progression of cancers. As a result of the illness, the consumption of some nutrients can be reduced, leading to nutritional deficiencies and resulting in malnutrition. Changes in metabolism may lead to cachexia in some patients suffering from NENs. The aim of this narrative review was to advance the knowledge in this area, and to determine possibilities related to dietary support. The authors also paid attention to role of biogenic amines in the treatment of patients with NENs. We can use this information to better understand nutritional issues faced by patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to help inform the development of screening tools and clinical practice guidelines.
Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study
Authors: E. Eleraky Nermin , M. Omar Mahmoud , A. Mahmoud Hemat , A. Abou-Taleb Heba
Published: May 2020

The opposing effect of the blood–brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, −10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.
Influence of the Degree of Cure in the Bulk Properties of Graphite Nanoplatelets Nanocomposites Printed via Stereolithography
Authors: De León Alberto S. , Molina Sergio I.
Published: May 2020

In this work, we report on the fabrication via stereolithography (SLA) of acrylic-based nanocomposites using graphite nanoplatelets (GNPs) as an additive. GNPs are able to absorb UV–Vis radiation, thus blocking partial or totally the light path of the SLA laser. Based on this, we identified a range of GNP concentrations below 2.5 wt %, where nanocomposites can be successfully printed. We show that, even though GNP is well-dispersed along the polymeric matrix, nanocomposites presented lower degrees of cure and therefore worse mechanical properties when compared with pristine resin. However, a post-processing at 60 °C with UV light for 1 h eliminates this difference in the degree of cure, reaching values above 90% in all cases. In these conditions, the tensile strength is enhanced for 0.5 wt % GNP nanocomposites, while the stiffness is increased for 0.5–1.0 wt % GNP nanocomposites. Finally, we also demonstrate that 2.5 wt % GNP nanocomposites possess characteristic properties of semiconductors, which allows them to be used as electrostatic dispersion materials.
Rheology in the Presence of Carbon Dioxide (CO2) to Study the Melt Behavior of Chemically Modified Polylactide (PLA)
Authors: Dörr Dominik , Standau Tobias , Murillo Castellón Svenja , Bonten Christian , Altstädt Volker
Published: May 2020

For the preparation of polylactide (PLA)-based foams, it is commonly necessary to increase the melt strength of the polymer. Additives such as chain extenders (CE) or peroxides are often used to build up the molecular weight by branching or even crosslinking during reactive extrusion. Furthermore, a blowing agent with a low molecular weight, such as carbon dioxide (CO2), is introduced in the foaming process, which might affect the reactivity during extrusion. Offline rheological tests can help to measure and better understand the kinetics of the reaction, especially the reaction between the polymer and the chemical modifier. However, rheological measurements are mostly done in an inert nitrogen atmosphere without an equivalent gas loading of the polymer melt, like during the corresponding reactive extrusion process. Therefore, the influence of the blowing agent itself is not considered within these standard rheological measurements. Thus, in this study, a rheometer equipped with a pressure cell is used to conduct rheological measurements of neat and chemical-modified polymers in the presence of CO2 at pressures up to 40 bar. The specific effects of CO2 at elevated pressure on the reactivity between the polymer and the chemical modifiers (an organic peroxide and as second choice, an epoxy-based CE) were investigated and compared. It could be shown in the rheological experiments that the reactivity of the chain extender is reduced in the presence of CO2, while the peroxide is less affected. Finally, it was possible to detect the recrystallization temperature Trc of the unmodified and unbranched sample by the torque maximum in the rheometer, representing the tear off of the stamp from the sample. Trc was about 13 K lower in the CO2-loaded sample. Furthermore, it was possible to detect the influences of branching and gas loading simultaneously. Here the influence of the branching on Trc was much higher in comparison to a gas loading.