bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium Alginate as a Potential Therapeutic Filler: An In Vivo Study in Rats
Authors: Mori Masanori , Asahi Rintaro , Yamamoto Yoshihiro , Mashiko Takanobu , Yoshizumi Kayo , Saito Natsumi , Shirado Takako , Wu Yunyan , Yoshimura Kotaro
Published: October 2020

Filler injection demand is increasing worldwide, but no ideal filler with safety and longevity currently exists. Sodium alginate (SA) is the sodium salt of alginic acid, which is a polymeric polysaccharide obtained by linear polymerization of two types of uronic acid, d-mannuronic acid (M) and l-guluronic acid (G). This study aimed to evaluate the therapeutic value of SA. Nine SA types with different M/G ratios and viscosities were tested and compared with a commercially available sodium hyaluronate (SH) filler. Three injection modes (onto the periosteum, intradermally, or subcutaneously) were used in six rats for each substance, and the animals were sacrificed at 4 or 24 weeks. Changes in the diameter and volume were measured macroscopically and by computed tomography, and histopathological evaluations were performed. SA with a low M/G ratio generally maintained skin uplift. The bulge gradually decreased over time but slightly increased at 4 weeks in some samples. No capsule formation was observed around SA. However, granulomatous reactions, including macrophage recruitment, were observed 4 weeks after SA implantation, although fewer macrophages and granulomatous reactions were observed at 24 weeks. The long-term volumizing effects and degree of granulomatous reactions differed depending on the M/G ratio and viscosity. By contrast, SH showed capsule formation but with minimal granulomatous reactions. The beneficial and adverse effects of SA as a filler differed according to the viscosity or M/G ratio, suggesting a better long-term volumizing effect than SH with relatively low immunogenicity
Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients
Authors: Curcio Annalisa , Romano Adriana , Cuozzo Simona , Di Nicola Antonio , Grassi Orazio , Schiaroli Donatella , Nocera Giuseppe Fabrizio , Pironti Michele
Published: October 2020

Background and Objectives: Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging cause of hepatopathy that is showing an increasing trend and where the recommendations of lifestyle modification are often not sufficient. The aim of this study is to evaluate the efficacy and tolerability profile of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) by analyzing liver enzymes, along with the lipidic profile, as markers of liver function, and ultrasound results in NAFLD patients. Materials and Methods: This study enrolled 81 patients with mild to severe NAFLD, divided into two groups: Group A (N = 41) received two capsules a day of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®), and Group B (N = 40) received only recommendations for lifestyle modification including hypocaloric diet, physical exercise and encouragement for weight loss. Patients have been evaluated at three timepoints: baseline (T0), after 45 days of treatment (T1) and after 90 days of treatment (T2), by collecting blood parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and the lipid blood profile. Ultrasonographic results have been analyzed at T0 and T2, along with the tolerability profile and side effects, registered at time T2. Results: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective since it showed a significant reduction of the evaluated parameters of ALT, AST, ALP and GGT, a significant improvement of lipid parameters, evaluated as markers of liver function, and improvements of ultrasonographic results. The use of this formulation at the dosage of two capsules a day has been well tolerated and no adverse events have been reported during study period of three months. Conclusions: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective and well tolerated in the improvement of hepatic function of NAFLD patients.
Modestly Elevated Serum Procalcitonin Levels in Patients with Rheumatoid Arthritis Free of Active Infection
Authors: Ng Khai-Jing , Yu Hui-Chun , Huang Tseng Hsien-Yu , Hsu Chia-Wen , Lu Ming-Chi
Published: October 2020

Background and objectives: To investigate the serum procalcitonin (PCT) levels among patients with rheumatoid arthritis (RA) without active infection compared with healthy controls and to understand the relationship of PCT with RA disease activity, and treatment received by patients. Materials and Methods: Patients aged 20 years and above with clinician-confirmed diagnosis of RA and healthy volunteers were included during regular outpatient visits, and those with active infection symptoms and signs were excluded. RA disease activity was measured using the Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (DAS28-ESR). Medications received by the patients were also recorded. Results: A total of 623 patients with RA and 87 healthy subjects were recruited in this study. The mean PCT were significantly higher in patients with RA (6.90 ± 11.81 × 10−3 ng/mL) compared with healthy controls (1.70 ± 6.12 × 10−3 ng/mL) (p < 0.001) and the difference remained statistically significant after adjusting for age and sex. In addition, multiple linear regression analysis showed that a lower rank-transformed PCT serum level was significantly correlated with the use of biologics (p = 0.017) and a high DAS28-ESR score (p = 0.028) in patients with RA. Conclusion: Patients with RA have a significantly higher serum PCT levels compared with healthy controls. The use of biologics and an active RA disease activity were associated with a lower level of PCT in patients with RA. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA and its association with disease activity and biologic usage.
Enhanced Fouling Resistance and Antimicrobial Property of Ultrafiltration Membranes Via Polyelectrolyte-Assisted Silver Phosphate Nanoparticle Immobilization
Authors: Olimattel Kunal , Church Jared , Lee Woo , Chumbimuni-Torres Karin , Zhai Lei , Sadmani A
Published: October 2020

Ultrafiltration (UF) is a low-pressure membrane that yields higher permeate flux and saves significant operating costs compared to high-pressure membranes; however, studies addressing the combined improvement of anti-organic and biofouling properties of UF membranes are lacking. This study investigated the fouling resistance and antimicrobial property of a UF membrane via silver phosphate nanoparticle (AgPNP) embedded polyelectrolyte (PE) functionalization. Negatively charged polyacrylic acid (PAA) and positively charged polyallylamine hydrochloride (PAH) were deposited on the membrane using a fluidic layer-by-layer assembly technique. AgPNPs were immobilized within the crosslinked “bilayers” (BL) of PAH/PAA. The effectiveness of AgPNP immobilization was confirmed by microprofile measurements on membrane surfaces using a solid contact Ag micro-ion-selective electrode. Upon stable and uniform BL formation on the membrane surface, the permeate flux was governed by a combined effect of PAH/PAA-derived hydrophilicity and surface/pore coverage by the BLs “tightening” of the membrane. When fouled by a model organic foulant (humic acid), the functionalized membrane exhibited a lower flux decline and a greater flux recovery due to the electrostatic repulsion imparted by PAA when compared to the unmodified membrane. The functionalization rendered antimicrobial property, as indicated by fewer attachments of bacteria that initiate the formation of biofilms leading to biofouling.
Targeted Metabolomic Profiling of Total Fatty Acids in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Aidaros Anas Al , Sharma Charu , Langhans Claus-Dieter , G. Okun Jürgen , Hoffmann Georg F. , Dasouki Majed , Chakraborty Pranesh , Aljasmi Fatma , Y. Al-Dirbashi Osama
Published: October 2020

This article reports a targeted metabolomic method for total plasma fatty acids (FAs) of clinical or nutritional relevance. Thirty-six saturated, unsaturated, or branched-chain FAs with a chain length of C8-C28 were quantified using reversed-phase liquid chromatography-tandem mass spectrometry. FAs in plasma (10 μL) were acid-hydrolyzed, extracted, and derivatized with DAABD-AE (4-[2-(N,N-Dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole) at 60 °C for 1 h. Derivatization resulted in a staggering nine orders of magnitude higher sensitivity compared to underivatized analytes. FAs were measured by multiple-reaction monitoring using stable isotope internal standards. With physiological and pathological analyte levels in mind, linearity was established using spiked plasma. Intra-day (n = 15) and inter-day (n = 20) imprecisions expressed as variation coefficient were ≤10.2% with recovery ranging between 94.5–106.4%. Limits of detection and limit of quantitation ranged between 4.2–14.0 and 15.1–51.3 pmol per injection, respectively. Age-stratified reference intervals were established in four categories: <1 month, 1–12 month, 1–18 year, and >18 year. This method was assessed using samples from patients with disorders affecting FAs metabolism. For the first time, C28:0 and C28:0/C22:0 ratio were evaluated as novel disease biomarkers. This method can potentially be utilized in diagnosing patients with inborn errors of metabolism, chronic disease risk estimation, or nutritional applications.
An Integrated Analytical Approach Reveals Trichome Acylsugar Metabolite Diversity in the Wild Tomato Solanum pennellii
Authors: Lybrand Daniel B. , Anthony Thilani M. , Jones A. Daniel , Last Robert L.
Published: October 2020

Acylsugars constitute an abundant class of pest- and pathogen-protective Solanaceae family plant-specialized metabolites produced in secretory glandular trichomes. Solanum pennellii produces copious triacylated sucrose and glucose esters, and the core biosynthetic pathway producing these compounds was previously characterized. We performed untargeted metabolomic analysis of S. pennellii surface metabolites from accessions spanning the species range, which indicated geographic trends in the acylsugar profile and revealed two compound classes previously undescribed from this species, tetraacylglucoses and flavonoid aglycones. A combination of ultrahigh-performance liquid chromatography–high resolution mass spectrometry (UHPLC–HR-MS) and NMR spectroscopy identified variations in the number, length, and branching pattern of acyl chains, and the proportion of sugar cores in acylsugars among accessions. The new dimensions of acylsugar variation revealed by this analysis further indicate variation in the biosynthetic and degradative pathways responsible for acylsugar accumulation. These findings provide a starting point for deeper investigation of acylsugar biosynthesis, an understanding of which can be exploited through crop breeding or metabolic engineering strategies to improve the endogenous defenses of crop plants.
Serum Metabonomic Research of the Anti-Hypertensive Effects of Ogaja on Spontaneously Hypertensive Rats
Authors: Yoon Dahye , Choi Bo-Ram , Lee Young-Seob , Han Kyung-Sook , Kim Donghwi , Lee Dae Young
Published: October 2020

Our previous studies have shown that Ogaja Acanthopanax sessiliflorus has an important role in decreasing blood pressure, but its biochemical change characteristic has not been clarified completely at the metabolic level. Therefore, in this study, a combination method of nuclear magnetic resonance (NMR) spectroscopy-based metabonomics and multivariate statistical analyses was employed to explore the metabolic changes of serum samples from spontaneously hypertensive rats treated with Ogaja extracts. In the results of multivariate statistical analysis, the spontaneously hypertensive rat (SHR) groups treated with Ogaja were separated from the SHR group. The group of SHR treated with 200 mg/kg Ogaja was clustered with the positive control (captopril) group, and the 400 and 600 mg/kg Ogaja treatment SHR groups were clustered together. Quantified metabolites were statistically analyzed to find the metabolites showing the effects of Ogaja. Succinate and betaine had variable importance in projection (VIP) scores over 2.0. Succinate, which is related to renin release, and betaine, which is related to lowering blood pressure, increased dose-dependently.
Metabolomic Alteration in the Mouse Distal Colonic Mucosa after Oral Gavage with Oxalobacter formigenes
Authors: Chamberlain Casey A. , Hatch Marguerite , Garrett Timothy J.
Published: October 2020

Oxalobacter formigenes has been investigated for years due to its proposed ability to produce a secretagogue compound that initiates net intestinal oxalate secretion, thereby theoretically reducing circulating oxalate and risk of kidney stone formation. Strains which have been shown to exhibit this function in vivo across native tissue include the human strain, HC1, and the wild rat strain, OxWR. While previous work on these secretagogue-relevant strains has focused on profiling their metabolome and lipidome in vitro, efforts to characterize their influence on host intestinal mucosal biochemistry in vivo are yet to be reported. Much work has been done over the years with O. formigenes in relation to the secretagogue hypothesis, but it has never been clearly demonstrated that this microorganism is capable of inducing metabolic changes in native host tissue, which would be expected with the production of a transport-inducing compound. In this work, we show how the distal colonic mucosal metabolomic profile in a mouse model exhibited significant changes in the levels of a variety of metabolites as a result of oral gavage with O. formigenes HC1. Among these significant metabolites was nicotinic acid, an essential nutrient shown in past work to be produced in the gut by the native microbiome. Our finding that the in vivo biochemical state of the distal colon was altered with O. formigenes lends support to the secretagogue hypothesis and serves as a pioneering step in characterizing the biochemical interplay between O. formigenes and the mammalian host.
Revisiting the Complex Pathosystem of Huanglongbing: Deciphering the Role of Citrus Metabolites in Symptom Development
Authors: Nehela Yasser , Killiny Nabil
Published: October 2020

Huanglongbing (HLB), formerly known as citrus greening disease, is one of the most devastating bacterial diseases in citrus worldwide. HLB is caused by ‘Candidatus Liberibacter asiaticus’ bacterium and transmitted by Diaphorina citri. Both ‘Ca. L. asiaticus’ and its vector manipulate the host metabolism to fulfill their nutritional needs and/or to neutralize the host defense responses. Herein, we discuss the history of HLB and the complexity of its pathosystem as well as the geographical distribution of its pathogens and vectors. Recently, our recognition of physiological events associated with ‘Ca. L. asiaticus’ infection and/or D. citri-infestation has greatly improved. However, the roles of citrus metabolites in the development of HLB symptoms are still unclear. We believe that symptom development of HLB disease is a complicated process and relies on a multilayered metabolic network which is mainly regulated by phytohormones. Citrus metabolites play vital roles in the development of HLB symptoms through the modulation of carbohydrate metabolism, phytohormone homeostasis, antioxidant pathways, or via the interaction with other metabolic pathways, particularly involving amino acids, leaf pigments, and polyamines. Understanding how ‘Ca. L. asiaticus’ and its vector, D. citri, affect the metabolic pathways of their host is critical for developing novel, sustainable strategies for HLB management.
A Python-Based Pipeline for Preprocessing LC–MS Data for Untargeted Metabolomics Workflows
Authors: Riquelme Gabriel , Zabalegui Nicolás , Marchi Pablo , Jones Christina M. , Monge María Eugenia
Published: October 2020

Preprocessing data in a reproducible and robust way is one of the current challenges in untargeted metabolomics workflows. Data curation in liquid chromatography–mass spectrometry (LC–MS) involves the removal of biologically non-relevant features (retention time, m/z pairs) to retain only high-quality data for subsequent analysis and interpretation. The present work introduces TidyMS, a package for the Python programming language for preprocessing LC–MS data for quality control (QC) procedures in untargeted metabolomics workflows. It is a versatile strategy that can be customized or fit for purpose according to the specific metabolomics application. It allows performing quality control procedures to ensure accuracy and reliability in LC–MS measurements, and it allows preprocessing metabolomics data to obtain cleaned matrices for subsequent statistical analysis. The capabilities of the package are shown with pipelines for an LC–MS system suitability check, system conditioning, signal drift evaluation, and data curation. These applications were implemented to preprocess data corresponding to a new suite of candidate plasma reference materials developed by the National Institute of Standards and Technology (NIST; hypertriglyceridemic, diabetic, and African-American plasma pools) to be used in untargeted metabolomics studies in addition to NIST SRM 1950 Metabolites in Frozen Human Plasma. The package offers a rapid and reproducible workflow that can be used in an automated or semi-automated fashion, and it is an open and free tool available to all users.
Emerging Role of Metabolomics in Ovarian Cancer Diagnosis
Authors: Saorin Asia , Di Gregorio Emanuela , Miolo Gianmaria , Steffan Agostino , Corona Giuseppe
Published: October 2020

Ovarian cancer is considered a silent killer due to the lack of clear symptoms and efficient diagnostic tools that often lead to late diagnoses. Over recent years, the impelling need for proficient biomarkers has led researchers to consider metabolomics, an emerging omics science that deals with analyses of the entire set of small-molecules (≤1.5 kDa) present in biological systems. Metabolomics profiles, as a mirror of tumor–host interactions, have been found to be useful for the analysis and identification of specific cancer phenotypes. Cancer may cause significant metabolic alterations to sustain its growth, and metabolomics may highlight this, making it possible to detect cancer in an early phase of development. In the last decade, metabolomics has been widely applied to identify different metabolic signatures to improve ovarian cancer diagnosis. The aim of this review is to update the current status of the metabolomics research for the discovery of new diagnostic metabolomic biomarkers for ovarian cancer. The most promising metabolic alterations are discussed in view of their potential biological implications, underlying the issues that limit their effective clinical translation into ovarian cancer diagnostic tools.
Shrinkage-Considered Mold Design for Improvement of Micro/Nano-Structured Optical Element Performance
Authors: Kim Minsu , Oh Eun Song , Kwak Moon Kyu
Published: October 2020

Polymer shrinkage in nano-imprint lithography (NIL) is one of the critical issues that must be considered in order to produce a quality product. Especially, this condition should be considered during the manufacture of optical elements, because micro/nano-structured optical elements should be controlled to fit the desired shape in order to achieve the intended optical performance. In this paper, during NIL, we characterized the shrinkage of polymeric resin on micro lens array (MLA), which is one of the representative micro/nano-structured optical elements. The curvature shape and optical performance of MLA were measured to check the shrinkage tendency during the process. The master mold of MLA was generated by the two-photon polymerization (2PP) additive manufacturing method, and the tested samples were replicated from the master mold with NIL. Several types of resin were adjusted to prepare the specimens, and the shrinkage effects in each case were compared. The shrinkage showed different trends based on the NIL materials and MLA shapes. These characterizations can be applied to compensate for the MLA design, and the desired performance of MLA products can be achieved with a corrected master mold.
Micro-Fabrication of Components for a High-Density Sub-Retinal Visual Prosthesis
Authors: Shire Douglas , Gingerich Marcus , Wong Patricia , Skvarla Michael , Cogan Stuart , Chen Jinghua , Wang Wei , Rizzo Joseph
Published: October 2020

We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School’s teaching hospital, the Massachusetts Eye and Ear—and later at the startup company Bionic Eye Technologies, by some of the same personnel. These efforts culminated in the fabrication and assembly of 256+ channel visual prosthesis devices having flexible multi-electrode arrays that were successfully implanted sub-retinally in mini-pig animal models as part of our pre-clinical testing program. We report on the processing of the flexible multi-layered, planar and penetrating high-density electrode arrays, surgical tools for sub-retinal implantation, and other parts such as coil supports that facilitated the implantation of the peri-ocular device components. We begin with an overview of the implantable portion of our visual prosthesis system design, and describe in detail the micro-fabrication methods for creating the parts of our system that were assembled outside of our hermetically-sealed electronics package. We also note the unique surgical challenges that sub-retinal implantation of our micro-fabricated components presented, and how some of those issues were addressed through design, materials selection, and fabrication approaches.
Dissolution, Stability and Solubility of Tooeleite [Fe6(AsO3)4(SO4)(OH)4·4H2O] at 25–45 °C and pH 2–12
Authors: Zhu Zongqiang , Zhang Jun , Zhu Yinian , Liu Jie , Tang Shen , Zhang Lihao , Wang Yaru
Published: October 2020

Tooeleite [Fe6(AsO3)4(SO4)(OH)4·4H2O] was synthesized and characterized to investigate its possible immobilization for arsenic in acidic and alkali environments by a long-term dissolution of 330 d. The synthetic tooeleite was platy crystallites of ~1μm across, giving the lattice parameters of a = 6.4758 Å, b = 19.3737 Å and c = 8.9170 Å. For the tooeleite dissolution, the dissolved arsenic concentration showed the lowest value of 427.3~435.8 mg/L As at initial pH 12 (final pH 5.54). The constituents were dissolved preferentially in the sequence of SO42− > AsO33− > Fe3+ in the aqueous medium at initial pH 2–12. The dissolved iron, arsenite and sulfate existed mainly as FeSO4+/Fe3+, H3AsO30 and SO42− at initial pH 2, and in the form of Fe(OH)30/Fe(OH)2+, H3AsO30 and SO42− at initial pH 12, respectively. The tooeleite dissolution was characterized by the preferential releases of SO42− anions from solid surface into aqueous medium, which was fundamentally controlled by the Fe-O/OH bond breakages and the outer OH− group layers. From the data of the dissolution at 25 °C and initial pH 2 for 270–330 d, the ion-activity product [logˍIAP], which equaled the solubility product [Ksp] at the dissolution equilibrium, and the Gibbs free energy of formation [ΔGfo] were estimated as −200.28 ± 0.01 and −5180.54 ± 0.07 kJ/mol for the synthetic tooeleite, respectively.
Influence of Solid Content, Cement/Tailings Ratio, and Curing Time on Rheology and Strength of Cemented Tailings Backfill
Authors: Li Jiajian , Yilmaz Erol , Cao Shuai
Published: October 2020

Understanding the flow process of cemented tailings backfill (CTB) is important for successful pumping into underground stopes. This study examines the effects of solid content (SC), cement/tailings (c/t) ratio, and curing time (CT) on rheological and mechanical properties of CTB mixes. The slurry concentration of the mixes was 65, 67, and 69 wt. %, with c/t ratios ranging from 1:4 to 1:20. Unconfined compressive strength (UCS) tests were performed on hardened CTB mixes after curing 3, 7, and 28 days. The rheological properties of CTB slurries are mainly related to SC. The yield stress and viscosity of fresh mixes increase with increasing SC, but the pipeline resistance loss (PRL) also increases with increasing SC. According to the analysis of variance, the SC and flow rate are the most significant parameters which greatly affect the PRL performance. The c/t and CT parameters are the most significant parameters for affecting the shrinkage rate. The findings offer a reference for theoretical optimization for mine filling systems of similar type.
Structural Modifications of Single-Crystal Aragonite CaCO3 Beginning at ~15 GPa: In Situ Vibrational Spectroscopy and X-Ray Diffraction Evidence
Authors: Gao Jing , Liu Yungui , Wu Xiang , Yuan Xueyin , Liu Yingxin , Su Wen
Published: October 2020

The structural chemistry of carbonates under mantle conditions facilitates our understanding of carbon recycling pathways in the earth’s interior. It also has impacts on the dynamics of mantle–slab interactions. Aragonite is a common calcium carbonate mineral in pelagic marine sediments. The structural chemistry of single-crystal aragonite during successive compression and the behavior of a structural H+ have been investigated by micro-vibrational spectroscopy and synchrotron X-ray diffraction techniques in diamond anvil cells. We describe a reduction of the b-axial compressibility beginning at ~15 GPa, and the related discontinuities in the first-order derivatives of the vibrational modes. The structural modifications of aragonite are manifested by mutations occurring in the pressure relations of the wavenumbers of the O-C-O bending modes, and of the bandwidth and band intensities of the measured internal and external modes. These anomalies are indicative of changes occurring in the force constant of the C-O bonds, and possibly a second-order phase transition. Besides, the [CaO9] polyhedra begin to deform, possibly with some Ca-O bonds becoming elongated and the others shortening. An increase in the co-ordination number for the Ca2+ sites could be expected under higher pressures. Additionally, the weakening of the OH modes may imply H+-loss from the aragonite lattice above 11.5 GPa.
Water Extract of Lotus Leaf Alleviates Dexamethasone-Induced Muscle Atrophy via Regulating Protein Metabolism-Related Pathways in Mice
Authors: Park Sang Hee , Oh Jieun , Jo Minkyeong , Kim Jin Kyeong , Kim Dong Seon , Kim Han Gyung , Yoon Keejung , Yang Yoonyong , Geum Jeong-ho , Kim Jung-Eun , Choi Su-Young , Kim Ji Hye , Cho Jae Youl
Published: October 2020

Muscle atrophy is an abnormal condition characterized by loss of skeletal muscle mass and function and is primarily caused by injury, malnutrition, various diseases, and aging. Leaf of lotus (Nelumbo nucifera Gaertn), which has been used for medicinal purposes, contains various active ingredients, including polyphenols, and is reported to exert an antioxidant effect. In this study, we investigated the effect of water extract of lotus leaf (LL) on muscle atrophy and the underlying molecular mechanisms of action. Amounts of 100, 200, or 300 mg/kg/day LL were administered to dexamethasone (DEX)-induced muscle atrophy mice for 4 weeks. Micro-computed tomography (CT) analysis revealed that the intake of LL significantly increased calf muscle volume, surface area, and density in DEX-induced muscle atrophy mice. Administration of LL recovered moving distance, grip strength, ATP production, and body weight, which were decreased by DEX. In addition, muscle damage caused by DEX was also improved by LL. LL reduced the protein catabolic pathway by suppressing gene expression of muscle atrophy F-Box (MAFbx; atrogin-1), muscle RING finger 1 (MuRF1), and forkhead box O (FoxO)3a, as well as phosphorylation of AMP-activated kinase (AMPK). The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. The HPLC analysis and pharmacological test revealed that quercetin 3-O-beta-glucuronide (Q3G) is a major active component in LL. Thus, Q3G decreased the gene expression of atrogin-1 and MuRF1 and phosphorylation of AMPK. This compound also increased phosphorylation levels of mTOR and its upstream enzyme AKT in DEX-treated C2C12 cells. We identified that LL improves muscle wasting through regulation of muscle protein metabolism in DEX-induced muscle atrophy mice. Q3G is predicted to be one of the major active phenolic components in LL. Therefore, we propose LL as a supplement or therapeutic agent to prevent or treat muscle wasting, such as sarcopenia.
Investigating the Modes of Action of the Antimicrobial Chalcones BC1 and T9A
Authors: Morão Luana G. , Lorenzoni André S. G. , Chakraborty Parichita , Ayusso Gabriela M. , Cavalca Lucia B. , Santos Mariana B. , Marques Beatriz C. , Dilarri Guilherme , Zamuner Caio , Regasini Luis O. , Ferreira Henrique , Scheffers Dirk-Jan
Published: October 2020

Xanthomonas citri subsp. citri (X. citri) is an important phytopathogen and causes Asiatic Citrus Canker (ACC). To control ACC, copper sprays are commonly used. As copper is an environmentally damaging heavy metal, new antimicrobials are needed to combat citrus canker. Here, we explored the antimicrobial activity of chalcones, specifically the methoxychalcone BC1 and the hydroxychalcone T9A, against X. citri and the model organism Bacillus subtilis. BC1 and T9A prevented growth of X. citri and B. subtilis in concentrations varying from 20 µg/mL to 40 µg/mL. BC1 and T9A decreased incorporation of radiolabeled precursors of DNA, RNA, protein, and peptidoglycan in X. citri and B. subtilis. Both compounds mildly affected respiratory activity in X. citri, but T9A strongly decreased respiratory activity in B. subtilis. In line with that finding, intracellular ATP decreased strongly in B. subtilis upon T9A treatment, whereas BC1 increased intracellular ATP. In X. citri, both compounds resulted in a decrease in intracellular ATP. Cell division seems not to be affected in X. citri, and, although in B. subtilis the formation of FtsZ-rings is affected, a FtsZ GTPase activity assay suggests that this is an indirect effect. The chalcones studied here represent a sustainable alternative to copper for the control of ACC, and further studies are ongoing to elucidate their precise modes of action.
Full-Spectrum Analysis of Bioactive Compounds in Rosemary (Rosmarinus officinalis L.) as Influenced by Different Extraction Methods
Authors: Sharma Yashaswini , Velamuri Ravikishore , Fagan John , Schaefer Jim
Published: October 2020

Rosmarinus officinalis is a potent antioxidant herb rich in polyphenols. Ultra-high-performance liquid chromatography, coupled with electrospray ionization and quadrupole-time of flight mass spectrometry (UHPLC-ESI-QTOF-MS), enables an exhaustive, full-spectrum analysis of the molecular constituents of natural products. The study aimed to develop a rapid UHPLC method to contribute new insights into the phytochemical composition of rosemary and to assess the performance of nine different procedures for extraction. These include fresh tissue homogenization, fresh and dry leaf decoction, and their respective fermentation, Soxhlet extraction, and sonication using water and methanol. Different extraction methods were found to recover quite different groups of polyphenols within 11 min during 20 min of analysis. Soxhlet extraction, yielded very high concentrations of rosmarinic acid (33,491.33 ± 86.29 µg/g), luteolin-7-O-glucoside (209.95 ± 8.78 µg/g), carnosic acid (2915.40 ± 33.23 µg/g), carnosol (22,000.67 ± 77.39 µg/g), and ursolic acid (5144.27 ± 28.68 µg/g). UHPLC-ESI-QTOF-MS enabled the detection of more than 50 polyphenols, including phenolic acids, flavonoids, and terpenoids in the various extracts. Of these, sagerinic acid ([M − H]−m/z 719.16), salvianolic acid A ([M − H]−m/z 493.11) and B ([M − H]−m/z 717.15), and a pentacyclic triterpenoid corosolic acid ([M − H]−m/z 471.34) were detected for the first time in rosemary. Soxhlet extraction was found to be the most efficient method, followed by dry leaf decoction. The UHPLC-ESI-QTOF-MS methodology for the analysis proved to be very efficient in the identification and characterization of targeted and untargeted bioactive molecules in the rosemary.
Electrochemotherapy Using Doxorubicin and Nanosecond Electric Field Pulses: A Pilot in Vivo Study
Authors: Novickij Vitalij , Malyško Veronika , Želvys Augustinas , Balevičiūtė Austėja , Zinkevičienė Auksė , Novickij Jurij , Girkontaitė Irutė
Published: October 2020

Pulsed electric field (PEF) is frequently used for intertumoral drug delivery resulting in a well-known anticancer treatment—electrochemotherapy. However, electrochemotherapy is associated with microsecond range of electrical pulses, while nanosecond range electrochemotherapy is almost non-existent. In this work, we analyzed the feasibility of nanosecond range pulse bursts for successful doxorubicin-based electrochemotherapy in vivo. The conventional microsecond (1.4 kV/cm × 100 µs × 8) procedure was compared to the nanosecond (3.5 kV/cm × 800 ns × 250) non-thermal PEF-based treatment. As a model, Sp2/0 tumors were developed. Additionally, basic current and voltage measurements were performed to detect the characteristic conductivity-dependent patterns and to serve as an indicator of successful tumor permeabilization both in the nano and microsecond pulse range. It was shown that nano-electrochemotherapy can be the logical evolution of the currently established European Standard Operating Procedures for Electrochemotherapy (ESOPE) protocols, offering better energy control and equivalent treatment efficacy.
Nutritional Enhancement of Farmed Salmon Meat via Non-GMO Nannochloropsis Gaditana: Eicosapentaenoic Acid (EPA, 20:5 n-3), Docosapentaenoic Acid (DPA, 22:5 n-3) and Vitamin D3 for Human Health
Authors: Lozano-Muñoz Ivonne , Muñoz Susana , Díaz Nelson F. , Medina Alberto , Bazaes Jazmín , Riquelme Carlos
Published: October 2020

Omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and vitamin D3 are essential components of human nutrition. A regular human diet is highly deficient in n-3 LC PUFAs. Fish like salmon are highly recommended in the human diet as they are a major source of high-value n-3 LC PUFAs and vitamin D3. The levels of these nutrients have been decreasing over the last few years in farmed salmon, whose production urgently needs sustainable sources of these nutrients. The microalga Nannochloropsis gaditana (NG) is known for its naturally high potential for the production of eicosapentaenoic (EPA, 20:5 n-3) fatty acid. A commercial diet for Atlantic salmon was supplemented with 1% and 10% of spray-dried NG grown under controlled conditions for a high EPA content. Salmon were harvested on day 49, following which, boneless and skinless salmon meat was recovered from fish and analyzed for the fatty acid profile, total fat, and vitamin D3. Vitamin D3, EPA, and docosapentaenoic fatty acid (DPA, 22:5 n-3) levels were significantly increased (p < 0.05) by supplementing the basal diet with 10% NG, thus, NG represents a novel, functional, natural ingredient and a sustainable source of n-3 LC-PUFAs that can raise the levels of healthy fats and vitamin D3 in farmed salmon meat.
Silver Fir (Abies alba L.) Polyphenolic Extract Shows Beneficial Influence on Chondrogenesis In Vitro under Normal and Inflammatory Conditions
Authors: Sirše Mateja , Fokter Samo K. , Štrukelj Borut , Zupan Janja
Published: October 2020

Several plant polyphenols have been shown to reduce osteoarthritis symptoms due to their antioxidant, anti-inflammatory and immunomodulatory properties. We investigated the effects of two different polyphenolic extracts (Belinal, Pycnogenol) and two different polyphenols (resveratrol, quercetin) on the chondrogenic potential of bone-derived mesenchymal stem/stromal cells (MSCs) from healthy donors and patients with osteoarthritis. Our main aim was to determine whether Belinal, a commercially available polyphenolic extract from silver fir (Abies alba L.) branches, has comparable chondrogenic potential with the other tested extract and the polyphenols under inflammatory and non-inflammatory conditions. In our study, Belinal promoted significantly greater chondrogenesis compared to the untreated (p = 0.0289) and resveratrol-treated (p = 0.0468) MSCs from patients with hip osteoarthritis under non-inflammatory conditions. Under inflammatory conditions, chondrogenesis was significantly enhanced for MSCs treated with Belinal compared to the control (p = 0.0483). The other extract and the polyphenols did not show any significant effects on chondrogenesis under non-inflammatory or inflammatory conditions. None of the tested extracts and polyphenols showed significant effects on chondrogenesis in healthy donors, under either non-inflammatory or inflammatory conditions. Our data show that Belinal can boost the chondrogenesis of MSCs derived from patients with osteoarthritis, under both non-inflammatory and inflammatory conditions.
Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway
Authors: Lim Eun Yeong , Park Joon , Kim Yun Tai , Kim Min Jung
Published: October 2020

Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway. While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels. Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/β, p-inhibitor of κB (IκBα), and p-p65. Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1).
Identification of Novel Thiazolo[5,4-b]Pyridine Derivatives as Potent Phosphoinositide 3-Kinase Inhibitors
Authors: Xia Liang , Zhang Yan , Zhang Jingbo , Lin Songwen , Zhang Kehui , Tian Hua , Dong Yi , Xu Heng
Published: October 2020

A series of novel 2-pyridyl, 4-morpholinyl substituted thiazolo[5,4-b]pyridine analogues have been designed and synthesized in this paper. These thiazolo[5,4-b]pyridines were efficiently prepared in seven steps from commercially available substances in moderate to good yields. All of these N-heterocyclic compounds were characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) analysis and tested for phosphoinositide 3-kinase (PI3K) enzymatic assay. The results indicated that these N-heterocyclic compounds showed potent PI3K inhibitory activity, and the IC50 of a representative compound (19a) could reach to 3.6 nm. The structure−activity relationships (SAR) study showed that sulfonamide functionality was important for PI3Kα inhibitory activity, and 2-chloro-4-florophenyl sulfonamide (19b), or 5-chlorothiophene-2-sulfonamide (19c) showed potent inhibitory activity with a nanomolar IC50 value. The pyridyl attached to thiazolo[5,4-b]pyridine was another key structural unit for PI3Kα inhibitory potency, and replacement by phenyl lead to a significant decrease in activity. Enzymatic Inhibition results showed that compound 19a inhibited PI3Kα, PI3Kγ, or PI3Kδ with a nanomolar IC50 value, but its inhibitory activity on PI3Kβ was approximately 10-fold reduced. Further docking analysis revealed that the N-heterocyclic core of compound 19a was directly involved in the binding to the kinase through the key hydrogen bonds interaction.
C4-Alkylamination of C4-Halo-1H-1-tritylpyrazoles Using Pd(dba)2 or CuI
Authors: Usami Yoshihide , Tatsui Yuya , Yoneyama Hiroki , Harusawa Shinya
Published: October 2020

Alkylamino coupling reactions at the C4 positions of 4-halo-1H-1-tritylpyrazoles were investigated using palladium or copper catalysts. The Pd(dba)2 catalyzed C-N coupling reaction of aryl- or alkylamines, lacking a β-hydrogen atom, proceeded smoothly using tBuDavePhos as a ligand. As a substrate, 4-Bromo-1-tritylpyrazole was more effective than 4-iodo or chloro-1-tritylpyrazoles. Meanwhile, the CuI mediated C-N coupling reactions of 4-iodo-1H-1-tritylpyrazole were effective for alkylamines possessing a β-hydrogen atom.
Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides
Authors: Ochoa Steven , Milam Valeria T.
Published: October 2020

In the last three decades, oligonucleotides have been extensively investigated as probes, molecular ligands and even catalysts within therapeutic and diagnostic applications. The narrow chemical repertoire of natural nucleic acids, however, imposes restrictions on the functional scope of oligonucleotides. Initial efforts to overcome this deficiency in chemical diversity included conservative modifications to the sugar-phosphate backbone or the pendant base groups and resulted in enhanced in vivo performance. More importantly, later work involving other modifications led to the realization of new functional characteristics beyond initial intended therapeutic and diagnostic prospects. These results have inspired the exploration of increasingly exotic chemistries highly divergent from the canonical nucleic acid chemical structure that possess unnatural physiochemical properties. In this review, the authors highlight recent developments in modified oligonucleotides and the thrust towards designing novel nucleic acid-based ligands and catalysts with specifically engineered functions inaccessible to natural oligonucleotides.
Chemical Modifications of Porous Shape Memory Polymers for Enhanced X-ray and MRI Visibility
Authors: Fletcher Grace K. , Nash Landon D. , Graul Lance M. , Jang Lindy K. , Herting Scott M. , Wilcox Matthew D. , Touchet Tyler J. , Sweatt Ana Katarina , McDougall Mary P. , Wright Steven M. , Maitland Duncan J.
Published: October 2020

The goal of this work was to develop a shape memory polymer (SMP) foam with visibility under both X-ray and magnetic resonance imaging (MRI) modalities. A porous polymeric material with these properties is desirable in medical device development for applications requiring thermoresponsive tissue scaffolds with clinical imaging capabilities. Dual modality visibility was achieved by chemically incorporating monomers with X-ray visible iodine-motifs and MRI visible monomers with gadolinium content. Physical and thermomechanical characterization showed the effect of increased gadopentetic acid (GPA) on shape memory behavior. Multiple compositions showed brightening effects in pilot, T1-weighted MR imaging. There was a correlation between the polymeric density and X-ray visibility on expanded and compressed SMP foams. Additionally, extractions and indirect cytocompatibility studies were performed to address toxicity concerns of gadolinium-based contrast agents (GBCAs). This material platform has the potential to be used in a variety of medical devices.
Synthesis of a New Class of Spirooxindole–Benzo[b]Thiophene-Based Molecules as Acetylcholinesterase Inhibitors
Authors: Barakat Assem , Alshahrani Saeed , Al-Majid Abdullah Mohammed , Ali M. , Altowyan Mezna Saleh , Islam Mohammad Shahidul , Alamary Abdullah Saleh , Ashraf Sajda , Ul-Haq Zaheer
Published: October 2020

A series of new oxindole-based spiro-heterocycles bearing the benzo[b]thiophene motif were synthesized via a 1,3-dipolar cycloaddition reaction and their acetylcholinesterase (AChE) inhibitory activity was evaluated. All the synthesized compounds exhibited moderate inhibitory activities against AChE, while IIc was found to be the most active analog with an IC50 value of 20,840 µM·L−1. Its molecular structure was a 5-chloro-substituted oxindole bearing benzo[b]thiophene and octahydroindole moieties. Based on molecular docking studies, IIc was strongly bound to the catalytic and peripheral anionic sites of the protein through hydrophilic, hydrophobic, and π-stacking interactions with Asp74, Trp86, Tyr124, Ser125, Glu202, Ser203, Trp236, Trp286, Phe297, Tyr337, and Tyr341. These interactions also indicated that the multiplicity of the IIc aromatic core significantly favored its activity.
Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells
Authors: Schoeman Recardia , Beukes Natasha , Frost Carminita
Published: October 2020

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.