bluuebunny/crossref_metadata_2025 huggingface dataset:
Adding Zooplankton to the OSMAC Toolkit: Effect of Grazing Stress on the Metabolic Profile and Bioactivity of a Diatom
Authors: Osvik Renate Døving , Ingebrigtsen Richard Andre , Norrbin Maria Fredrika , Andersen Jeanette Hammer , Eilertsen Hans Christian , Hansen Espen Holst
Published: February 2021

“One strain many compounds” (OSMAC) based approaches have been widely used in the search for bioactive compounds. Introducing stress factors like nutrient limitation, UV-light or cocultivation with competing organisms has successfully been used in prokaryote cultivation. It is known that diatom physiology is affected by changed cultivation conditions such as temperature, nutrient concentration and light conditions. Cocultivation, though, is less explored. Hence, we wanted to investigate whether grazing pressure can affect the metabolome of the marine diatom Porosira glacialis, and if the stress reaction could be detected as changes in bioactivity. P. glacialis cultures were mass cultivated in large volume bioreactor (6000 L), first as a monoculture and then as a coculture with live zooplankton. Extracts of the diatom biomass were screened in a selection of bioactivity assays: inhibition of biofilm formation, antibacterial and cell viability assay on human cells. Bioactivity was found in all bioassays performed. The viability assay towards normal lung fibroblasts revealed that P. glacialis had higher bioactivity when cocultivated with zooplankton than in monoculture. Cocultivation with diatoms had no noticeable effect on the activity against biofilm formation or bacterial growth. The metabolic profiles were analyzed showing the differences in diatom metabolomes between the two culture conditions. The experiment demonstrates that grazing stress affects the biochemistry of P. glacialis and thus represents a potential tool in the OSMAC toolkit.
Metabolites of Marine Sediment-Derived Fungi: Actual Trends of Biological Activity Studies
Authors: Yurchenko Anton N. , Girich Elena V. , Yurchenko Ekaterina A.
Published: February 2021

Marine sediments are characterized by intense degradation of sedimenting organic matter in the water column and near surface sediments, combined with characteristically low temperatures and elevated pressures. Fungi are less represented in the microbial communities of sediments than bacteria and archaea and their relationships are competitive. This results in wide variety of secondary metabolites produced by marine sediment-derived fungi both for environmental adaptation and for interspecies interactions. Earlier marine fungal metabolites were investigated mainly for their antibacterial and antifungal activities, but now also as anticancer and cytoprotective drug candidates. This review aims to describe low-molecular-weight secondary metabolites of marine sediment-derived fungi in the context of their biological activity and covers research articles published between January 2016 and November 2020.
Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression
Authors: Lee Hyo-Geun , Lu Yu-An , Je Jun-Geon , Jayawardena Thilina U. , Kang Min-Cheol , Lee Seung-Hong , Kim Tae-Hee , Lee Dae-Sung , Lee Jeong-Min , Yim Mi-Jin , Kim Hyun-Soo , Jeon You-Jin
Published: February 2021

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.
Bilateral Ultrathin Descemet’s Stripping Automated Endothelial Keratoplasty vs. Bilateral Penetrating Keratoplasty in Fuchs’ Dystrophy: Corneal Higher-Order Aberrations, Contrast Sensitivity and Quality of Life
Authors: Castellucci Massimo , Novara Costanza , Casuccio Alessandra , Cillino Giovannni , Giordano Carla , Failla Valentina , Bonfiglio Vincenza , Vadalà Maria , Cillino Salvatore
Published: February 2021

Background and Objectives: The objective of this paper is to compare the visual outcomes and quality of life (QoL) after bilateral ultrathin Descemet’s stripping automated endothelial keratoplasty (UT-DSAEK) with bilateral penetrating keratoplasty (PK) for Fuchs’ endothelial dystrophy (FED). Materials and Methods: Retrospective comparative cohort study, including 11 patients with FED who underwent bilateral PK and 13 patients with FED who underwent bilateral UT-DSAEK. All patients were already pseudophakic or had undergone a combined cataract procedure. The main outcomes were corrected distance visual acuity (CDVA) corneal higher-order aberrations (HOAs), contrast sensitivity (CS) and quality of life (QoL). Results: The mean follow-up after the second eye surgery was 32.5 ± 10.2 months in PK and 19.6 ± 8.6 months in UT-DSAEK patients. The CDVA in the UT-DSAEK group was significantly better than in the PK one (0.18 ± 0.07 vs. 0.35 ± 0.16 logMAR, p < 0.0001). The mean anterior corneal total HOAs of the central 5 mm were significantly lower in UT-DSAEK eyes than in PK eyes (0.438 ± 0.078 µ and 1.282 ± 0.330 µ respectively, p < 0.0001), whilst the mean posterior total HOAs did not differ between groups (0.196 ± 0.056 µ and 0.231 ± 0.089 µ, respectively, p = 0.253). The CS was lower at 0.75 and 1.5 cycles/degree in P the K group when compared to the DSAEK one (p = 0.008 and 0.005, respectively). The QoL scores by the NEI RQL-42 test exhibited better values in DSAEK patients in 9 out of 13 scales. Conclusion: Our study confirms that UT-DSAEK provides a better visual function in terms of CDVA and CS, together with lower HOAs, when compared to PK. Hence, the vision-related QoL, binocularly evaluated by the NEI RQL-42 items, indicates a higher satisfaction in UT-DSAEK eyes.
The Fertility Indicator Equation Using Serum Progesterone and Urinary Pregnanediol-3-Glucuronide for Assessment of Ovulatory to Luteal Phase Transition
Authors: Usala Stephen J. , Alliende María Elena , Trindade A. Alexandre
Published: February 2021

Background and Objectives: The Fertility Indicator Equation (FIE) has been shown to signal the fertile phase during the ovulatory menstrual cycle. It was hypothesized that this formulation, a product of two sequential normalized changes with a sign indicating direction of change, could be used to identify the transition from ovulatory to luteal phase with daily serum progesterone (P) and urinary pregnanediol-3-glucuronide (PDG) levels. Materials and Methods: Day-specific serum P levels from two different laboratories and day-specific urinary PDG levels from an additional two different laboratories were submitted for FIE analysis. These day-specific levels included mean or median, 5th, 10th, 90th and 95th percentile data. They were indexed to the day of ovulation, day 0, by ultrasonography, serum or urinary luteinizing hormone (LH). Results: All data sets showed a clear “cluster”—a periovulatory sequence of positive FIE values with a maximum. All clusters of +FIE signaled the transition from the ovulatory to luteal phase and were at least four days in length. The start day for the serum P and urinary PDG FIE clusters ranged from −3 to −1 and −3 to +2, respectively. The end day for serum P and PDG clusters went from +2 to +7 and +4 to +8, respectively. Outside these periovulatory FIE-P and FIE-PDG clusters, there were no consecutive positive FIE values. In addition, the maximum FIE-P and FIE-PDG values throughout the entire cycles were found in the clusters. Conclusions: FIE analysis with either daily serum P or urinary PDG levels provided a distinctive signature to recognize the periovulatory interval. The Fertility Indicator Equation served to robustly signal the transition from the ovulatory phase to the luteal phase. This may have applications in natural family planning especially with the recent emergence of home PDG tests.
Stem Cell Ophthalmology Treatment Study (SCOTS): Bone Marrow-Derived Stem Cells in the Treatment of Stargardt Disease
Authors: Weiss Jeffrey N. , Levy Steven
Published: February 2021

Background: Stargardt Disease is the most common inherited macular degeneration, typically resulting in progressive central vision loss and legal blindness at an early age. We report regarding 34 eyes with Stargardt Disease treated in the Stem Cell Ophthalmology Treatment Study (SCOTS and SCOTS2). Methods: Autologous bone marrow was processed, separating the stem cell fraction which was provided Arms using retrobulbar, subtenons, intravitreal or subretinal and intravenous. The follow-up period was one year. Results: Of the 34 treated eyes, 21 (61.8%) improved, 8 (23.5%) remained stable, and 5 (14.7%) showed continued progression of their disease. Results were statistically significant with p = 0.0004. The average central vision improvement following treatment was 17.96% (95%CI, 16.39–19.53%) and ranged up to 80.5%. Of 17 patients treated, 13 (76.5%) showed visual acuity improvement in one or both eyes, 3 patients (17.6%) showed no net loss, and 1 worsened as a consequence of disease progression; 94.1% of patients had improved vision or remained stable. There were no adverse events. Conclusions: Patients with Stargardt Disease may potentially benefit from autologous bone marrow-derived stem cells (BMSC) as provided in SCOTS. Improvement or stabilization of vision was found to occur for the vast majority of reported patients and findings were highly statistically significant.
Characterization of the Solid Particle Erosion of the Sealing Surface Materials of a Ball Valve
Authors: Peng Donghua , Dong Shaohua , Wang Zhiqiang , Wang Dongying , Chen Yinuo , Zhang Laibin
Published: February 2021

The ball valve is an essential piece of equipment in an oil and gas pipeline. The sand particles transported through the pipeline can cause erosion and wear to the ball valve, thus causing it to fail, leading to serious safety hazards. In this paper, the self-designed erosion experiment method was combined with computational fluid dynamics (CFD), while the Euler-Lagrange method was also introduced to optimize the Oka erosion model and Ford particle-wall rebound model. The erosion mechanism and characteristics of the ball valve sealing surface in gas-solid two-phase flow were simulated, while the erosion condition of the specimen was analyzed and compared when exposed to different factors, such as different particle velocities, impact angle, particle size, and specimen materials. The experimental data conformed well to the CFD erosion simulation data, verifying the accuracy of the CFD simulation analysis. The results indicated that the worn surface was caused by various wear mechanisms, while a “stagnation zone” was identified at the center of the specimen. The maximum erosion area, which was U-shaped, was also located at the center. The erosion rate increased in conjunction with an increase in the particle velocity and size, both of which failed to affect the erosion pattern. The erosion rate initially increased, after which it decreased with the impact angle, reaching the maximum value at an impact angle of 30°. This paper summarizes the erosion failure mechanism and characteristics in gas–solid two-phase flow and provides both technical support and a theoretical basis for the on-site maintenance of essential vulnerable parts in the pipeline, such as ball valves.
A Novel Impedance Micro-Sensor for Metal Debris Monitoring of Hydraulic Oil
Authors: Zhang Hongpeng , Shi Haotian , Li Wei , Ma Laihao , Zhao Xupeng , Xu Zhiwei , Wang Chenyong , Xie Yucai , Zhang Yuwei
Published: February 2021

Hydraulic oil is the key medium for the normal operation of hydraulic machinery, which carries various wear debris. The information reflected by the wear debris can be used to predict the early failure of equipment and achieve predictive maintenance. In order to realize the real-time condition monitoring of hydraulic oil, an impedance debris sensor that can detect inductance and resistance parameters is designed and studied in this paper. The material and size of wear debris can be discriminated based on inductance-resistance detection method. Silicon steel strips and two rectangular channels are designed in the sensor. The silicon steel strips are used to enhance the magnetic field strength, and the double rectangular detection channels can make full use of the magnetic field distribution region, thereby improving the detection sensitivity and throughput of the sensor. The comparison experiment shows that the coils in series are more suitable for the monitoring of wear debris. By comparing and analyzing the direction and the presence or absence of the signal pulses, the debris sensor can detect and distinguish 46 µm iron particles and 110 µm copper particles. This impedance detection method provides a new technical support for the high-precision distinguishing measurement of metal debris. The sensor can not only be used for oil detection in the laboratory, but also can be made into portable oil detection device for machinery health monitoring.
Navigation Grade MEMS IMU for A Satellite
Authors: Zhao Wanliang , Cheng Yuxiang , Zhao Sihan , Hu Xiaomao , Rong Yijie , Duan Jie , Chen Jiawei
Published: February 2021

This paper presents a navigation grade micro-electromechanical system (MEMS) inertial measurement unit (IMU) that was successfully applied for the first time in the Lobster-Eye X-ray Satellite in July 2020. A six-axis MEMS gyroscope redundant configuration is adopted in the unit to improve the performance through mutual calibration of a set of two-axis gyroscopes in the same direction. In the paper, a satisfactory precision of the gyroscope is achieved by customized and self-calibration gyroscopes whose parameters are adjusted at the expense of bandwidth and dynamics. According to the in-orbit measured data, the MEMS IMU provides an outstanding precision of better than 0.02 °/h (1σ) with excellent bias instability of 0.006 °/h and angle random walk (ARW) of around 0.003 °/h1/2. It is the highest precision MEMS IMU for commercial aerospace use ever publicly reported in the world to date.
Fundamental Studies of Rapidly Fabricated On-Chip Passive Micromixer for Modular Microfluidics
Authors: Guo Wenpeng , Tang Li , Zhou Biqiang , Fung Yingsing
Published: February 2021

Micromixers play an important role in many modular microfluidics. Complex on-chip mixing units and smooth channel surfaces ablated by lasers on polymers are well-known problems for microfluidic chip fabricating techniques. However, little is known about the ablation of rugged surfaces on polymer chips for mixing uses. This paper provides the first report of an on-chip compact micromixer simply, easily and quickly fabricated using laser-ablated irregular microspheric surfaces on a polymethyl methacrylate (PMMA) microfluidic chip for continuous mixing uses in modular microfluidics. The straight line channel geometry is designed for sequential mixing of nanoliter fluids in about 1 s. The results verify that up to about 90% of fluids can be mixed in a channel only 500 µm long, 200 µm wide and 150 µm deep using the developed micromixer fabricating method under optimized conditions. The computational flow dynamics simulation and experimental result agree well with each other.
Numerical Study of the Microflow Characteristics in a V-ball Valve
Authors: Gao Zhi-xin , Yue Yang , Yang Jia-ming , Li Jun-ye , Wu Hui , Jin Zhi-jiang
Published: February 2021

V-ball valves are widely applied in many process industries to regulate fluid flow, and they have advantages of good approximately equal percentage flow characteristics and easy maintenance. However, in some applications, the V-ball valve needs to have good performance under both large and extremely small flow coefficients. In this paper, the improvement of the original V-ball valve is made and the flow characteristics between the original and the improved V-ball valve are compared. Two types of small gaps are added to the original V-ball, namely the gap with an approximately rectangular port and the gap with an approximately triangular port. The effects of the structure and the dimension of the gap on flow characteristics are investigated. Results show that within the gap, the flow coefficient increases but the loss coefficient decreases as the valve opening increases, and the flow coefficient has an approximately linear relationship with the flow cross-area of the added gap. Results also show that under the same flow cross-area, the flow coefficient has a higher value if the distance between the gap and the ball center is greater or if the gap is an approximately rectangular port, while the loss coefficient has an opposite trend.
Coumarin Sulfonamides and Amides Derivatives: Design, Synthesis, and Antitumor Activity In Vitro
Authors: Zhang Jing , Tan Yaling , Li Guorong , Chen Lexian , Nie Minyi , Wang Zhaohua , Ji Hong
Published: February 2021

Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC50 value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.
Pharmacological Extracts and Molecules from Virola Species: Traditional Uses, Phytochemistry, and Biological Activity
Authors: González-Rodríguez María , Ruiz-Fernández Clara , Francisco Vera , Ait Eldjoudi Djedjiga , Farrag AbdElHafez Yousof Ramadan , Cordero-Barreal Alfonso , Pino Jesus , Lago Francisca , Campos-Toimil Manuel , Rocha Carvalho Glaucimeire , Melo Costa Pereira Thiago , Gualillo Oreste
Published: February 2021

Virola is the largest genus of Myristicaceae in America, comprising about 60 species of medium-sized trees geographically spread from Mexico to southern Brazil. The plant species of this genus have been widely used in folk medicine for the treatment of several ailments, such as rheumatic pain, bronchial asthma, tumors in the joints, intestinal worms, halitosis, ulcers, and multiple infections, due to their pharmacological activity. This review presents an updated and comprehensive summary of Virola species, particularly their ethnomedicinal uses, phytochemistry, and biological activity, to support the safe medicinal use of plant extracts and provide guidance for future research. The Virola spp.’s ethnopharmacology, including in the treatment of stomach pain and gastric ulcers, as well as antimicrobial and tryponosomicidal activities, is attributable to the presence of a myriad of phytoconstituents, such as flavonoids, tannins, phenolic acids, lignans, arylalkanones, and sitosterol. Hence, such species yield potential leads or molecular scaffolds for the development of new pharmaceutical formulations, encouraging the elucidation of not-yet-understood action mechanisms and ascertaining their safety for humans.
A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan
Authors: Di Rong , Liu Jingwen , Grohganz Holger , Rades Thomas
Published: February 2021

Converting crystalline compounds into co-amorphous systems is an effective way to improve the solubility of poorly water-soluble drugs. It is, however, of critical importance for the physical stability of co-amorphous systems to find the optimal mixing ratio of the drug with the co-former. In this study, a novel approach for this challenge is presented, exemplified with the co-amorphous system carvedilol–tryptophan (CAR–TRP). Following X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) of the ball-milled samples to confirm their amorphous form, Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were applied to investigate intermolecular interactions. A clear deviation from a purely additive spectrum of CAR and TRP was visualized in the PCA score plot, with a maximum at around 30% drug (mol/mol). This deviation was attributed to hydrogen bonds of CAR with TRP ether groups. The sample containing 30% drug (mol/mol) was also the most stable sample during a stability test. Using the combination of FTIR with PCA is an effective approach to investigate the optimal mixing ratio of non-strong interacting co-amorphous systems.
Spin Hamiltonians in Magnets: Theories and Computations
Authors: Li Xueyang , Yu Hongyu , Lou Feng , Feng Junsheng , Whangbo Myung-Hwan , Xiang Hongjun
Published: February 2021

The effective spin Hamiltonian method has drawn considerable attention for its power to explain and predict magnetic properties in various intriguing materials. In this review, we summarize different types of interactions between spins (hereafter, spin interactions, for short) that may be used in effective spin Hamiltonians as well as the various methods of computing the interaction parameters. A detailed discussion about the merits and possible pitfalls of each technique of computing interaction parameters is provided.
Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis
Authors: Zhang Rui , Ni Leng , Di Xiao , Ma Baitao , Niu Shuai , Rong Zhihua , Liu Changwei
Published: February 2021

Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid artery and further reduce the arterial lumen. Ischemic stroke due to severe CAS and cerebral ischemic/reperfusion (I/R) injury after the revascularization of CAS also adversely affect clinical outcomes. Melatonin is a pluripotent agent with potent anti-inflammatory, anti-oxidative, and neuroprotective properties. Although there is a shortage of direct clinical evidence demonstrating the benefits of melatonin in CAS patients, previous studies have shown that melatonin may be beneficial for patients with CAS in terms of reducing endothelial damage, stabilizing arterial plaque, mitigating the harm from CAS-related ischemic stroke and cerebral I/R injury, and alleviating the adverse effects of the related risk factors. Additional pre-clinical and clinical are required to confirm this speculation.
Comparison of Three Accelerated Oxidation Tests Applied to Red Wines with Different Chemical Composition
Authors: Coppola Francesca , Picariello Luigi , Forino Martino , Moio Luigi , Gambuti Angelita
Published: February 2021

Background: Three accelerated oxidation tests were proposed to simulate red wine oxidation thus providing information useful to correctly manage moderate oxygen exposure of wine during aging in regard to phenolic composition and wine color. Since the results of the tests have never been compared on wines with different initial composition, the aim of this study was to find a suitable method to simulate oxidation of any still red wine. Methods: Aglianico, Barbera, Gaglioppo, Magliocco, and Nerello wines were treated with (1) three cycles of air saturation, (2) the addition of hydrogen peroxide, and (3) the addition of acetaldehyde. Changes in chromatic characteristics and phenolic composition were determined by spectrophotometric and HPLC methods. Results: Important differences in the behavior of the different wines were detected: the highest formation of polymeric pigments was observed in Barbera and Aglianico wines. In contrast, Gaglioppo and Magliocco wines showed a lower variability before and after the oxidation probably due to the lower anthocyanin/tannin ratio. Among the accelerated oxidation tests applied, no significant differences in color parameters and phenolic composition were detected in samples treated with the addition of H2O2 and the air saturation method. Conclusion: The study demonstrated that H2O2 addition is a successful tool to predict the evolution of different phenolic compounds during the air saturation treatment of wines.
Determination of Cytotoxic Activity of Selected Isoquinoline Alkaloids and Plant Extracts Obtained from Various Parts of Mahonia aquifolium Collected in Various Vegetation Seasons
Authors: Tuzimski Tomasz , Petruczynik Anna , Kaproń Barbara , Makuch-Kocka Anna , Szultka-Młyńska Małgorzata , Misiurek Justyna , Szymczak Grażyna , Buszewski Bogusław
Published: February 2021

Melanoma is a serious form of skin cancer that begins in cells known as melanocytes. While it is less common than the other forms of skin cancer, melanoma is more dangerous because of its ability to spread to other organs more rapidly if it is not treated at an early stage. The number of people diagnosed with melanoma has increased over the last few decades. The most widely used treatments include surgery, chemotherapy, and radiation therapy. The search for new drugs to treat various cancers is one of the most important challenges of modern scientific research. Some isoquinoline alkaloids found in different plant species have strong cytotoxic effects on various cancer cells. We tested the effect of isoquinoline alkaloids and extracts obtained from various parts of Mahonia aquifolium collected in various vegetation seasons on human melanoma cancer cells and our data indicated that investigated extract induced significant reduction in cell viability of Human malignant melanoma cells (A375), human Caucasian malignant melanoma cell line (G361), and human malignant melanoma cell line (SKMEL3 cancer cell lines in a dose- and time-dependent manner. Differences in cytotoxic activity were observed for extracts obtained from various parts of Mahonia aquifolium. Significant differences were also obtained in the alkaloids content and cytotoxic activity of the extracts depending on the season of collection of plant material. Our investigations exhibit that these plant extracts can be recommended for further in vivo experiments in order to confirm the possibility of their use in the treatment of human melanomas.
A Korean-Style Balanced Diet Has a Potential Connection with Ruminococcaceae Enterotype and Reduction of Metabolic Syndrome Incidence in Korean Adults
Authors: Wu Xuangao , Unno Tatsuya , Kang Suna , Park Sunmin
Published: February 2021

Metabolic syndrome is associated with usual dietary patterns that may be involved in enterotypes. We aimed to understand the potential relationship of enterotypes and dietary patterns to influence metabolic syndrome in the Koreans. Using the Korea National Health and Nutrition Examination Survey (KNHANES)-VI in 2014, metabolic parameters were also analyzed among the dietary patterns classified by principal component analysis in Korean adults. The fecal microbiota data of 1199 Korean adults collected in 2014 were obtained from the Korea Centers for Disease Control and Prevention. Enterotypes were classified based on Dirichlet multinomial mixtures (DMM) by Mothur v.1.36. The functional abundance of fecal bacteria was analyzed using the PICRUSt2 pipeline. Korean adults were clustered into three dietary patterns including Korean-style balanced diets (KBD, 20.4%), rice-based diets (RBD, 17.2%), and Western-style diets (WSD, 62.4%) in KNHANES. The incidence of metabolic syndrome was lowered in the order of RBD, WSD, and KBD. The participants having a KBD had lower serum C-reactive protein and triglyceride concentrations than those with RBD and WSD (p < 0.05). Three types of fecal bacteria were classified as Ruminococcaceae type (ET-R, 28.7%), Prevotella type (ET-P, 52.2%), and Bacteroides type (ET-B, 42.1%; p < 0.05). ET-P had a higher abundance of Prevotella copri, while ET-R contained a higher abundance of Alistipes, Akkermansia muciniphila, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. ET-B had a higher abundance of the order Bilophila (p < 0.05). Metabolism of propanoate, starch, and sucrose in fecal microbiome was higher in ET-P and ET-R, whereas fatty acid metabolism was enhanced in ET-B. Fecal microbiota in ET-P and ET-B had higher lipopolysaccharide biosynthesis activity than that in ET-R. The metabolic results of KBD and RBD were consistent with ET-R and ET-P’s gut microbiota metabolism, respectively. In conclusion, Korean enterotypes of ET-P, ET-B, and ET-R were associated with RBD, WSD, and KBD, respectively. This study suggests a potential link between dietary patterns, metabolic syndrome, and enterotypes among Korean adults.
Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice
Authors: Yang Jinchunzi , Sáinz Neira , Félix-Soriano Elisa , Gil-Iturbe Eva , Castilla-Madrigal Rosa , Fernández-Galilea Marta , Martínez J. Alfredo , Moreno-Aliaga María J.
Published: February 2021

Obesity and aging are associated to non-alcoholic fatty liver disease (NAFLD) development. Here, we investigate whether long-term feeding with a docosahexaenoic acid (DHA)-enriched diet and aerobic exercise, alone or in combination, are effective in ameliorating NAFLD in aged obese mice. Two-month-old female C57BL/6J mice received control or high fat diet (HFD) for 4 months. Then, the diet-induced obese (DIO) mice were distributed into four groups: DIO, DIO + DHA (15% dietary lipids replaced by a DHA-rich concentrate), DIO + EX (treadmill running), and DIO + DHA + EX up to 18 months. The DHA-rich diet reduced liver steatosis in DIO mice, decreasing lipogenic genes (Dgat2, Scd1, Srebp1c), and upregulated lipid catabolism genes (Hsl/Acox) expression. A similar pattern was observed in the DIO + EX group. The combination of DHA + exercise potentiated an increase in Cpt1a and Ppara genes, and AMPK activation, key regulators of fatty acid oxidation. Exercise, alone or in combination with DHA, significantly reversed the induction of proinflammatory genes (Mcp1, Il6, Tnfα, Tlr4) in DIO mice. DHA supplementation was effective in preventing the alterations induced by the HFD in endoplasmic reticulum stress-related genes (Ern1/Xbp1) and autophagy markers (LC3II/I ratio, p62, Atg7). In summary, long-term DHA supplementation and/or exercise could be helpful to delay NAFLD progression during aging in obesity.
Yogurt Consumption Is Associated with Lower Levels of Chronic Inflammation in the Framingham Offspring Study
Authors: Yuan Mengjie , Singer Martha R. , Moore Lynn L.
Published: February 2021

Some studies suggest that dairy foods may be linked with less chronic inflammation. However, few studies have investigated the separate effects of different types of dairy on inflammation. Therefore, the current study aims to examine the separate prospective impacts of milk, yogurt and cheese on biomarkers of chronic inflammation in 1753 community-dwelling participants of the Framingham Offspring Study (FOS). Mean intakes of dairy foods were derived from two sets of three-day diet records. Six inflammatory biomarkers were assessed approximately seven years later at exam 7. Results showed that those who consumed yogurt (vs. those who did not) had statistically significantly lower levels of interleukin-6 (IL-6) (mean log-transformed levels of 1.31 and 1.26 in consumers/non-consumers, respectively, p = 0.02) and fibrin (mean log-transformed levels of 5.91 and 5.89 in consumers/non-consumers, respectively, p = 0.03). The inverse association between IL-6 and yogurt consumption was similar in participants who were of normal weight and those who were overweight. For fibrin, the effects were stronger in overweight individuals. No statistically significant associations were observed between any of these inflammation biomarkers and milk or cheese intakes. Overall, our study compared the separate impacts of three types of dairy foods on chronic inflammation and found that only yogurt intake was linked with lower levels of chronic inflammation.
The Gut Microbiome and Metabolomics Profiles of Restricting and Binge-Purging Type Anorexia Nervosa
Authors: Monteleone Alessio Maria , Troisi Jacopo , Serena Gloria , Fasano Alessio , Dalle Grave Riccardo , Cascino Giammarco , Marciello Francesca , Calugi Simona , Scala Giovanni , Corrivetti Giulio , Monteleone Palmiero
Published: February 2021

Alterations in the gut microbiome and fecal metabolites have been detected in anorexia nervosa (AN), but differences in those profiles between restricting AN (ANR) and binge-purging AN (ANBP) type have not been explored. We made a secondary analysis of our previous data concerning microbiome and metabolomics profiles of 17 ANR women, six ANBP women and 20 healthy controls (HC). Twelve fecal metabolites differentiating ANR patients, ANBP patients and HC were identified. Both patient groups showed decreased intra-individual bacterial richness with respect to healthy controls (HC). Compared to ANR subjects, ANBP patients had a significant increase in relative abundances of Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, and Eubacteriacae and a significant decrease in relative abundances of Odoribacter, Haemophilus, Pasteurellaceae, and Pasteurellales. The heatmaps of the relationships of selected fecal metabolites with microbial families showed different structures among the three groups, with the heatmap of ANBP patients being drastically different from that of HC, while that of ANR patients resulted more similar to HC. These findings, although preliminary because of the relatively small sample size, confirm the occurrence of different gut dysbiosis in ANR and ANBP and demonstrate different connections between gut microorganisms and fecal metabolites in the two AN types.
The Influence of Dysphagia on Nutritional and Frailty Status among Community-Dwelling Older Adults
Authors: Nishida Takahiro , Yamabe Kazumi , Honda Sumihisa
Published: February 2021

Malnutrition is a core symptom of the frailty cycle in older adults. The purpose of this study was to investigate whether dysphagia influences nutrition or frailty status in community-dwelling older adults. The study participants were 320 Japanese community-dwelling older adults aged ≥65 years. All participants completed a questionnaire survey that included items on age, sex, family structure, self-rated health, nutritional and frailty status, and swallowing function. Nutritional status was categorized as malnourished, at risk of malnutrition, and well-nourished based on the Mini Nutrition Assessment-Short Form. The participants were then classified into a malnutrition (malnourished/at risk) or a well-nourished group (well-nourished). Frailty was assessed using the Cardiovascular Health Study criteria. The participants were then divided into a frailty (frail/pre-frail) or a non-frailty group (robust). Dysphagia was screened using the 10-item Eating Assessment Tool. Multiple logistic regression analysis was conducted to determine whether dysphagia was associated with nutritional or frailty status. The results revealed that dysphagia influenced both nutrition (odds ratio [OR]: 4.0; 95% confidence interval [CI]: 1.9–8.2) and frailty status (OR: 2.3; 95% CI: 1.0–5.2); therefore, the swallowing function would be an important factor for community-dwelling older adults on frailty prevention programs.
Is There an Ideal Diet to Protect against Iodine Deficiency?
Authors: Krela-Kaźmierczak Iwona , Czarnywojtek Agata , Skoracka Kinga , Rychter Anna Maria , Ratajczak Alicja Ewa , Szymczak-Tomczak Aleksandra , Ruchała Marek , Dobrowolska Agnieszka
Published: February 2021

Iodine deficiency is a global issue and affects around 2 billion people worldwide, with pregnant women as a high-risk group. Iodine-deficiency prevention began in the 20th century and started with global salt iodination programmes, which aimed to improve the iodine intake status globally. Although it resulted in the effective eradication of the endemic goitre, it seems that salt iodination did not resolve all the issues. Currently, it is recommended to limit the consumption of salt, which is the main source of iodine, as a preventive measure of non-communicable diseases, such as hypertension or cancer the prevalence of which is increasing. In spite of the fact that there are other sources of iodine, such as fish, seafood, dairy products, water, and vegetables, the high consumption of processed food with a high content of unionised salt, alternative diets or limited salt intake can still lead to iodine deficiency. Thus, iodine deficiency remains a relevant issue, with new, preventive solutions necessary. However, it appears that there is no diet which would fully cover the iodine requirements, and iodine food supplementation is still required.
The Impact of Human Papillomavirus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) on Nutritional Outcomes
Authors: Harrowfield Jane , Isenring Elizabeth , Kiss Nicole , Laing Erin , Lipson-Smith Ruby , Britton Ben
Published: February 2021

Background: Patients undergoing (chemo) radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) are at high risk of malnutrition during and after treatment. Malnutrition can lead to poor tolerance to treatment, treatment interruptions, poor quality of life (QOL) and potentially reduced survival rate. Human papillomavirus (HPV) is now known as the major cause of OPSCC. However, research regarding its effect on nutritional outcomes is limited. The aim of this study was to examine the relationship between HPV status and nutritional outcomes, including malnutrition and weight loss during and after patients’ (chemo) radiotherapy treatment for OPSCC. Methods: This was a longitudinal cohort study comparing the nutritional outcomes of HPV-positive and negative OPSCC patients undergoing (chemo) radiotherapy. The primary outcome was nutritional status as measured using the Patient Generated-Subjective Global Assessment (PG-SGA). Secondary outcomes included loss of weight, depression, QOL and adverse events. Results: Although HPV-positive were less likely to be malnourished according to PG-SGA at the beginning of treatment, we found that the difference between malnutrition rates in response to treatment was not significantly different over the course of radiotherapy and 3 months post treatment. HPV-positive participants had significantly higher odds of experiencing >10% weight loss at three months post-treatment than HPV-negative participants (OR = 49.68, 95% CI (2.7, 912.86) p ≤ 0.01). Conclusions: The nutritional status of HPV positive and negative patients were both negatively affected by treatment and require similarly intense nutritional intervention. In acute recovery, HPV positive patients may require more intense intervention. At 3- months post treatment, both groups still showed nutritional symptoms that require nutritional intervention so ongoing nutritional support is essential.
Association of Lower Nutritional Status and Education Level with the Severity of Depression Symptoms in Older Adults—A Cross Sectional Survey
Authors: Chrzastek Zuzanna , Guligowska Agnieszka , Soltysik Bartlomiej , Pigłowska Malgorzata , Borowiak Ewa , Kostka Joanna , Kostka Tomasz
Published: February 2021

The study analyzes the relationship between nutritional status and depression symptoms severity in the older population. A total of 1975 older outpatients (1457 women and 518 men, median age 75) were included in the study. Depression symptoms severity was assessed using the Geriatric Depression Scale (GDS). Participants were divided into two subgroups according to GDS score. Group A: 0–5 points—without depression symptoms (1237, W:898, M:339), and group B: 6–15 points—with depression symptoms (738, W:559, M:179). The nutritional status of the patients was assessed with Mini Nutritional Assessment (MNA) and basic anthropometric variables (waist, hips, calf circumferences, body mass index (BMI), waist to hip ratio (WHR), and waist to height ratio (WHtR)). Education years and chronic diseases were also noted. Women with higher depression symptoms severity had significantly lower MNA scores [A: 26.5 (24–28) (median (25%−75% quartiles)) vs. B:23 (20.5–26)], shorter education time [A:12 (8–16) vs. B:7 (7–12)], smaller calf circumference [A:36 (33–38) vs. B: 34 (32–37)], and higher WHtR score [A:57.4 (52.3–62.9) vs. B:58.8 (52.1–65.6)]. Men with depression symptoms had lower MNA scores [A:26.5 (24.5–28) vs. B:24 (20.5–26.5)], shorter education [A:12 (9.5–16), B:10 (7–12)], and smaller calf circumference [A:37 (34–39), B:36 (33–38)]. In the model of stepwise multiple regression including age, years of education, anthropometric variables, MNA and concomitant diseases nutritional assessment, and education years were the only independent variables predicting severity of depression symptoms both in women and men. Additionally, in the female group, odds were higher with higher WHtR. Results obtained in the study indicate a strong relationship between proper nutritional status and education level with depression symptoms severity in older women and men.
Integrative Genomic–Epigenomic Analysis of Clozapine-Treated Patients with Refractory Psychosis
Authors: Mayén-Lobo Yerye Gibrán , Martínez-Magaña José Jaime , Pérez-Aldana Blanca Estela , Ortega-Vázquez Alberto , Genis-Mendoza Alma Delia , Dávila-Ortiz de Montellano David José , Soto-Reyes Ernesto , Nicolini Humberto , López-López Marisol , Monroy-Jaramillo Nancy
Published: February 2021

Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients with refractory psychosis, but it has also been proposed as an effective mood stabilizer; however, the complex mechanisms of action of CLZ are not yet fully known. To find predictors of CLZ-associated phenotypes (i.e., the metabolic ratio, dosage, and response), we explore the genomic and epigenomic characteristics of 44 patients with refractory psychosis who receive CLZ treatment based on the integration of polygenic risk score (PRS) analyses in simultaneous methylome profiles. Surprisingly, the PRS for bipolar disorder (BD-PRS) was associated with the CLZ metabolic ratio (pseudo-R2 = 0.2080, adjusted p-value = 0.0189). To better explain our findings in a biological context, we assess the protein–protein interactions between gene products with high impact variants in the top enriched pathways and those exhibiting differentially methylated sites. The GABAergic synapse pathway was found to be enriched in BD-PRS and was associated with the CLZ metabolic ratio. Such interplay supports the use of CLZ as a mood stabilizer and not just as an antipsychotic. Future studies with larger sample sizes should be pursued to confirm the findings of this study.
Electrochemical and Mechanistic Study of Superoxide Elimination by Mesalazine through Proton-Coupled Electron Transfer
Authors: Nakayama Tatsushi , Honda Ryo
Published: February 2021

The elimination of superoxide radical anions (O2•−) by 5-amino-2-hydroxybenzoic acid (mesalazine, 5-ASA), 4-amino-2-hydroxybenzoic acid (4-ASA), and related compounds used for ulcerative colitis treatment was investigated using cyclic voltammetry and electron spin resonance (ESR) analyses aided by density functional theory (DFT) calculations. Quasi-reversible O2/O2•− redox was found to be modified by the compounds, suggesting that an acid–base reaction in which a hydroperoxyl radical (HO2•) is formed from O2•− occurs. However, the deprotonated 5-ASA anion can eliminate O2•− through proton-coupled electron transfer (PCET), forming a radical product. This electron transfer (ET) was confirmed by ESR analysis. The 4-aminophenol moiety in 5-ASA plays an important role in the PCET, involving two proton transfers and one ET based on π-conjugation. The electrochemical and DFT results indicated that O2•− elimination by 5-ASA proceeds efficiently through the PCET mechanism after deprotonation of the 1-carboxyl group. Thus, 5-ASA may act as an anti-inflammatory agent in the alkali intestine through PCET-based O2•− elimination.
Formulation Considerations for the Management of Dry Eye Disease
Authors: Agarwal Priyanka , Craig Jennifer P. , Rupenthal Ilva D.
Published: February 2021

Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.