bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Inflammatory Effect of Phytoncide in an Animal Model of Gastrointestinal Inflammation
Authors: Memon Azra , Kim Bae Yong , Kim Se-eun , Pyao Yuliya , Lee Yeong-Geun , Kang Se Chan , Lee Woon Kyu
Published: March 2021

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.
An RP-LC-UV-TWIMS-HRMS and Chemometric Approach to Differentiate between Momordicabalsamina Chemotypes from Three Different Geographical Locations in Limpopo Province of South Africa
Authors: Venter Pieter , Malemela Kholofelo , Mbazima Vusi , Mampuru Leseilane J. , Muller Christo J. F. , Riedel Sylvia
Published: March 2021

Momordica balsamina leaf extracts originating from three different geographical locations were analyzed using reversed-phase liquid chromatography (RP-LC) coupled to travelling wave ion mobility (TWIMS) and high-resolution mass spectrometry (HRMS) in conjunction with chemometric analysis to differentiate between potential chemotypes. Furthermore, the cytotoxicity of the three individual chemotypes was evaluated using HT-29 colon cancer cells. A total of 11 molecular species including three flavonol glycosides, five cucurbitane-type triterpenoid aglycones and three glycosidic cucurbitane-type triterpenoids were identified. The cucurbitane-type triterpenoid aglycones were detected in the positive ionization mode following dehydration [M + H − H2O]+ of the parent compound, whereas the cucurbitane-type triterpenoid glycosides were primarily identified following adduct formation with ammonia [M + NH4]+. The principle component analysis (PCA) loadings plot and a variable influence on projection (VIP) analysis revealed that the isomeric pair balsaminol E and/or karavilagen E was the key molecular species contributing to the distinction between geographical samples. Ultimately, based on statistical analysis, it is hypothesized that balsaminol E and/or karavilagen E are likely responsible for the cytotoxic effects in HT-29 cells.
Chemical Diversity and Biological Activity of Secondary Metabolites Isolated from Indonesian Marine Invertebrates
Authors: Izzati Fauzia , Warsito Mega Ferdina , Bayu Asep , Prasetyoputri Anggia , Atikana Akhirta , Sukmarini Linda , Rahmawati Siti Irma , Putra Masteria Yunovilsa
Published: March 2021

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007–2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.
C2-Symmetric P-Stereogenic Ferrocene Ligands with Heavier Chalcogenophosphinous Acid Ester Donor Sites
Authors: Franz Roman , Bruhn Clemens , Pietschnig Rudolf
Published: March 2021

tert-Butyl-substituted diphospha[2]ferrocenophane was used as a stereochemically confined diphosphane to investigate the addition of various dichalcoganes (R2Ch2; Ch = S, Se, Te and R = Me, Ph). Bischalcogenophosphinous acid esters bearing four soft donor sides were obtained as a mixture of rac and meso diastereomers and characterized by means of multinuclear NMR and X-ray analysis. The coordination chemistry of multidentate ligand 3b was explored toward d10 coinage metal centers (Cu(I), Ag(I), and Au(I)), yielding various bimetallic complexes.
Evaluation of Antioxidant and Enzyme Inhibition Properties of Croton hirtus L’Hér. Extracts Obtained with Different Solvents
Authors: Dall’Acqua Stefano , Sinan Kouadio Ibrahime , Sut Stefania , Ferrarese Irene , Etienne Ouattara Katinan , Mahomoodally Mohamad Fawzi , Lobine Devina , Zengin Gokhan
Published: March 2021

Croton hirtus L’Hér methanol extract was studied by NMR and two different LC-DAD-MSn using electrospray (ESI) and atmospheric pressure chemical ionization (APCI) sources to obtain a quali-quantitative fingerprint. Forty different phytochemicals were identified, and twenty of them were quantified, whereas the main constituents were dihydro α ionol-O-[arabinosil(1-6) glucoside] (133 mg/g), dihydro β ionol-O-[arabinosil(1-6) glucoside] (80 mg/g), β-sitosterol (49 mg/g), and isorhamnetin-3-O-rutinoside (26 mg/g). C. hirtus was extracted with different solvents—namely, water, methanol, dichloromethane, and ethyl acetate—and the extracts were assayed using different in vitro tests. The methanolic extracts presented the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) values. All the tested extracts exhibited inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with a higher activity observed for dichloromethane (AChE: 5.03 and BChE: 16.41 mgGALAE/g), while the methanolic extract showed highest impact against tyrosinase (49.83 mgKAE/g). Taken together, these findings suggest C. hirtus as a novel source of bioactive phytochemicals with potential for commercial development.
Cold Plasma Systems and Their Application in Surface Treatments for Medicine
Authors: Tabares Francisco L. , Junkar Ita
Published: March 2021

In this paper, a review of cold plasma setups and the physical and chemical processes leading to the generation of active species is presented. The emphasis is given to the interaction of cold plasmas with materials used in medical applications, especially medical implants as well as live cells. An overview of the different kinds of plasmas and techniques used for generation of active species, which significantly alter the surface properties of biomaterials is presented. The elemental processes responsible for the observed changes in the physio-chemical properties of surfaces when exposed to plasma are described. Examples of ongoing research in the field are given to illustrate the state-of-the-art at the more conceptual level.
Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform
Authors: Chakravarty Kaushik , Antontsev Victor G. , Khotimchenko Maksim , Gupta Nilesh , Jagarapu Aditya , Bundey Yogesh , Hou Hypatia , Maharao Neha , Varshney Jyotika
Published: March 2021

The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.
Biosynthesis of Zinc Oxide Nanoparticles from Acacia nilotica (L.) Extract to Overcome Carbapenem-Resistant Klebsiella Pneumoniae
Authors: Rasha Elsayim , Monerah AlOthman , Manal Alkhulaifi , Rehab Ali , Mohammed Doud , Doaa Elnagar
Published: March 2021

Recently, concerns have been raised globally about antimicrobial resistance, the prevalence of which has increased significantly. Carbapenem-resistant Klebsiella pneumoniae (KPC) is considered one of the most common resistant bacteria, which has spread to ICUs in Saudi Arabia. This study was established to investigate the antibacterial activity of biosynthesized zinc oxide nanoparticles (ZnO-NPs) against KPC in vitro and in vivo. In this study, we used the aqueous extract of Acacia nilotica (L.) fruits to mediate the synthesis of ZnO-NPs. The nanoparticles produced were characterized by UV-vis spectroscopy, zetasizer and zeta potential analyses, X-ray diffraction (XRD) spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The antimicrobial activity of ZnO-NPs against KPC was determined via the well diffusion method, and determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the results showed low MIC and MBC when compared with the MIC and MBC of Imipenem and Meropenem antibiotics. The results of in vitro analysis were supported by the results upon applying ZnO-NP ointment to promote wound closure of rats, which showed better wound healing than the results with imipenem ointment. The biosynthesized ZnO-NPs showed good potential for use against bacteria due to their small size, applicability, and low toxicity to human cells.
Investigation into the Structural, Chemical and High Mechanical Reforms in B4C with Graphene Composite Material Substitution for Potential Shielding Frame Applications
Authors: Alarifi Ibrahim M.
Published: March 2021

In this work, boron carbide and graphene nanoparticle composite material (B4C–G) was investigated using an experimental approach. The composite material prepared with the two-step stir casting method showed significant hardness and high melting point attributes. Scanning electron microscopy (SEM), along with energy dispersive X-ray spectroscopy (EDS) analysis, indicated 83.65%, 17.32%, and 97.00% of boron carbide + 0% graphene nanoparticles chemical compositions for the C-atom, Al-atom, and B4C in the compound studied, respectively. The physical properties of all samples’ B4C–G like density and melting point were 2.4 g/cm3 density and 2450 °C, respectively, while the grain size of B4C–G was in the range of 0.8 ± 0.2 µm. XRD, FTIR, and Raman spectroscopic analysis was also performed to investigate the chemical compositions of the B4C–G composite. The molding press composite machine was a fabrication procedure that resulted in the formation of outstanding materials by utilizing the sintering process, including heating and pressing the materials. For mechanical properties, high fracture toughness and tensile strength of B4C–G composites were analyzed according to ASTM standard designs. The detailed analysis has shown that with 6% graphene content in B4C, the composite material portrays a high strength of 134 MPa and outstanding hardness properties. Based on these findings, it is suggested that the composite materials studied exhibit novel features suitable for use in the application of shielding frames.
A SERS Study of Charge Transfer Process in Au Nanorod–MBA@Cu2O Assemblies: Effect of Length to Diameter Ratio of Au Nanorods
Authors: Guo Lin , Mao Zhu , Jin Sila , Zhu Lin , Zhao Junqi , Zhao Bing , Jung Young Mee
Published: March 2021

Surface-enhanced Raman scattering (SERS) is a powerful tool in charge transfer (CT) process research. By analyzing the relative intensity of the characteristic bands in the bridging molecules, one can obtain detailed information about the CT between two materials. Herein, we synthesized a series of Au nanorods (NRs) with different length-to-diameter ratios (L/Ds) and used these Au NRs to prepare a series of core–shell structures with the same Cu2O thicknesses to form Au NR–4-mercaptobenzoic acid (MBA)@Cu2O core–shell structures. Surface plasmon resonance (SPR) absorption bands were adjusted by tuning the L/Ds of Au NR cores in these assemblies. SERS spectra of the core-shell structure were obtained under 633 and 785 nm laser excitations, and on the basis of the differences in the relative band strengths of these SERS spectra detected with the as-synthesized assemblies, we calculated the CT degree of the core–shell structure. We explored whether the Cu2O conduction band and valence band position and the SPR absorption band position together affect the CT process in the core–shell structure. In this work, we found that the specific surface area of the Au NRs could influence the CT process in Au NR–MBA@Cu2O core–shell structures, which has rarely been discussed before.
Anemia Prevalence and Anthropometric Status of Indigenous Women and Young Children in Rural Botswana: The San People
Authors: Leepile Tebogo T. , Mokomo Kaelo , Bolaane Maitseo M. M. , Jones Andrew D. , Takada Akira , Black Jennifer L. , Jovel Eduardo , Karakochuk Crystal D.
Published: March 2021

In Botswana, there is limited data available on the health and nutritional status of the San People (also known as the Basarwa or Bushmen), an Indigenous minority group primarily living in the Ghanzi District. Our aim in this study was to assess anemia prevalence among and anthropometric indices of women and young children in Ghanzi District through a cross-sectional survey. We recruited 367 mother–child pairs (women 15–49 years and children 6–59 months) in nine randomly selected areas. A capillary blood sample was collected, and weight and height were measured. Hemoglobin (Hb) concentration was measured with use of a hemoglobinometer (HemoCue, AB), as per global recommendations. Overall, adjusted anemia prevalence was 12% in non-pregnant women (Hb < 120 g/L), 26% in pregnant women (Hb < 110 g/L), and 42% in children (Hb < 110 g/L), but it varied widely depending on whether or not the controversial factor of ethnicity was adjusted for (range of 6–26%, 22–30%, and 35–68% prevalence, respectively). Thirty-nine percent (n = 133/344) of non-pregnant women and 52% (n = 12/23) of pregnant women were underweight (BMI < 18.5 kg/m2). In children aged 6–23 months, 41% were underweight (weight-for-age z-score < −2 SD), 13% were wasted (weight-for-height z-score < −2 SD), and 65% were stunted (height-for-age z-score < −2 SD); in children aged 24–59 months, 57% were underweight, 13% were wasted, and 66% were stunted. Fifty-six percent (n = 205/367) of women self-reported smoking in any form (rolled cigarettes or snuffing). The high prevalence of smoking among women, underweight status among pregnant women, and anemia, stunting, and wasting among children is of the highest concern for public health and should be addressed in future health and nutrition programming.
Gluten-Free Diet: Nutritional Strategies to Improve Eating Habits in Children with Celiac Disease: A Prospective, Single-arm Intervention Study
Authors: Suárez-González Marta , Bousoño-García Carlos , Jiménez-Treviño Santiago , Díaz-Martín Juan José
Published: March 2021

Background: Elimination of gluten-containing cereals and consumption of ultra-processed gluten-free foods might cause an unbalanced diet, deficient in fiber and rich in sugar and fat, circumstances that may predispose celiac children to chronic constipation. Aim: to evaluate if counseling with a registered dietitian (RD) was capable of improving eating and bowel habits in a celiac pediatric population. Methods: Dietetic, lipid profile and stool modifications were analyzed, comparing baseline assessments with those twelve months after receiving heathy eating and nutrition education sessions. At both time points, 3-day food records, a bowel habit record and a lipid panel were conducted. Calculated relative intake of macro- and micro-nutrients were compared with current recommendations by the European Food Safety Authority (EFSA). Student’s paired t-test, McNemar test, Mandasky test and Pearson correlation tests were used. Results: Seventy-two subjects (58.3% girls) with a mean (standard deviation (SD)) age of 10.2 (3.4) years were included. Baseline diets were imbalanced in macronutrient composition. Significant improvements were observed in their compliance with dietary reference values (DRVs), where 50% of the subjects met fat requirements after the education and 67% and 49% with those of carbohydrates and fiber, respectively (p < 0.001). Celiac children decreased red meat and ultra-processed foods consumption (p < 0.001) and increased fruits and vegetables intake (p < 0.001), leading to a reduction in saturated fat (p < 0.001) and sugar intake (p < 0.001). Furthermore, 92% of the patients achieved a normal bowel habit, including absence of hard stools in 80% of children constipated at baseline (p < 0.001). Conclusions: RD-led nutrition education is able to improve eating patterns in children with celiac disease (CD).
Food Fortification: The Advantages, Disadvantages and Lessons from Sight and Life Programs
Authors: Olson Rebecca , Gavin-Smith Breda , Ferraboschi Chiara , Kraemer Klaus
Published: March 2021

Deficiencies in one or more micronutrients such as iron, zinc, and vitamin A are widespread in low- and middle-income countries and compromise the physical and cognitive capacity of millions of people. Food fortification is a cost-effective strategy with demonstrated health, economic and social benefits. Despite ongoing debates globally and in some countries regarding the performance and safety of food fortification, the practice offers significant benefits across each of the main vehicles for food fortification (large-scale food fortification, biofortification and point-of-use or home fortification) ranging from reducing the prevalence of nutritional deficiencies and economic benefits to societies and economies. Using Sight and Life’s global and national experiences in implementing food fortification efforts, we demonstrate how different programs in LMICs have successfully addressed challenges with food fortification and in doing so, find that these efforts are most successful when partnerships are formed that include the public and private sector as well as other parties that can provide support in key areas such as advocacy, management, capacity building, implementation and regulatory monitoring.
Zinc Nutritional Status in a Series of Children with Chronic Diseases: A Cross-Sectional Study
Authors: Escobedo-Monge Marlene Fabiola , Torres-Hinojal María Carmen , Barrado Enrique , Escobedo-Monge María Antonieta , Marugán-Miguelsanz José Manuel
Published: March 2021

Background: Zinc is an essential trace element for the normal growth and development of human beings. The main objective was to evaluate the nutritional status of zinc and its association with nutritional indicators in a series of children with chronic diseases. Methods: The prevalence of patients with dietary zinc deficiency or deficit zinc intake (<80% DRI: dietary reference intake) was analyzed through prospective 72 h dietary surveys, and serum zinc deficiency or hypozincemia (≤70 µg/dL in children under 10 years of age in both sexes and in females older than 10 years and <74 μg/dL in males older than 10 years) was measured through atomic absorption spectrophotometry. The participants were classified according to their nutritional status by body mass index (BMI). Results: Mean serum zinc level in obese (87 µg/dL), undernourished (85 µg/dL), and eutrophic children (88 µg/dL) were normal, but in the undernutrition (60% DRI) and eutrophic (67% DRI) groups the mean dietary zinc intake was low compared to that in the obesity group (81% DRI). There were different associations between nutritional parameters, dietary zinc intake, and serum zinc. All patients with hypozincemia had dietary zinc deficiency. Conclusions: In the whole series, 69% of participants showed a zinc intake lower than recommended and might be at high risk of zinc deficiency.
Human Milk Microbiota and Oligosaccharides: A Glimpse into Benefits, Diversity, and Correlations
Authors: Moubareck Carole Ayoub
Published: March 2021

Human milk represents a cornerstone for growth and development of infants, with extensive array of benefits. In addition to exceptionally nutritive and bioactive components, human milk encompasses a complex community of signature bacteria that helps establish infant gut microbiota, contributes to maturation of infant immune system, and competitively interferes with pathogens. Among bioactive constituents of milk, human milk oligosaccharides (HMOs) are particularly significant. These are non-digestible carbohydrates forming the third largest solid component in human milk. Valuable effects of HMOs include shaping intestinal microbiota, imparting antimicrobial effects, developing intestinal barrier, and modulating immune response. Moreover, recent investigations suggest correlations between HMOs and milk microbiota, with complex links possibly existing with environmental factors, genetics, geographical location, and other factors. In this review, and from a physiological and health implications perspective, milk benefits for newborns and mothers are highlighted. From a microbiological perspective, a focused insight into milk microbiota, including origins, diversity, benefits, and effect of maternal diet is presented. From a metabolic perspective, biochemical, physiological, and genetic significance of HMOs, and their probable relations to milk microbiota, are addressed. Ongoing research into mechanistic processes through which the rich biological assets of milk promote development, shaping of microbiota, and immunity is tackled.
Farmed Mussels: A Nutritive Protein Source, Rich in Omega-3 Fatty Acids, with a Low Environmental Footprint
Authors: Yaghubi Elham , Carboni Stefano , Snipe Rhiannon M. J. , Shaw Christopher S. , Fyfe Jackson J. , Smith Craig M. , Kaur Gunveen , Tan Sze-Yen , Hamilton David. Lee
Published: March 2021

The world’s ever-growing population presents a major challenge in providing sustainable food options and in reducing pressures on the Earth’s agricultural land and freshwater resources. Current estimates suggest that agriculture contributes ~30% of global greenhouse gas (GHG) emissions. Additionally, there is an increased demand for animal protein, the production of which is particularly polluting. Therefore, the climate-disrupting potential of feeding the planet is likely to substantially worsen in the future. Due to the nutritional value of animal-based protein, it is not a simple solution to recommend a wholesale reduction in production/consumption of animal proteins. Rather, employing strategies which result in the production of low carbon animal protein may be part of the solution to reduce the GHGs associated with our diets without compromising diet quality. We suggest that farmed mussels may present a partial solution to this dilemma. Mussel production has a relatively low GHG production and does not put undue pressure on land or fresh water supplies. By drawing comparisons to other protein sources using the Australian Food and Nutrient Database and other published data, we demonstrate that they are a sustainable source of high-quality protein, long-chain omega-3 fatty acids, phytosterols, and other key micronutrients such as B-12 and iron. The aim of this review is to summarise the current knowledge on the health benefits and potential risks of increasing the consumption of farmed mussels.
Olanzapine Increases Neural Chemorepulsant—Draxin Expression in the Adult Rat Hippocampus
Authors: Pałasz Artur , Suszka-Świtek Aleksandra , Francikowski Jacek , Krzystanek Marek , Bogus Katarzyna , Skałbania Jakub , Worthington John J. , Mrzyk Inga
Published: March 2021

Draxin belongs to the family of inhibitory axon-guiding factors that regulate neuronal migration and axonal spreading in the developing brain. This glycoprotein has recently been considered to play an important role both in hippocampal differentiation and adult neurogenesis in the dentate gyrus. Given that it has been reported that antipsychotic drugs may affect neurite growth and neurogenesis, we have therefore investigated whether chronic treatment with olanzapine modulates draxin immunoreactivity in the adult rat hippocampus. After analysis of local fluorescence intensity, we found a significant increase of draxin immunoexpression both in the subgranular zone (SGZ) and granular zone of the rat hippocampus following long-term olanzapine administration. This study reveals, for the first time, the modulatory effect of the atypical antipsychotic medication olanzapine on expression of the novel chemorepulsive protein draxin in the context of adult neurogenesis regulation. Moreover, this is the first report dealing with pharmacological aspects of draxin signaling. An elevated draxin expression may indirectly support a recently formulated hypothesis that olanzapine may drive adult neurogenesis via paracrine draxin-related signaling. This action of draxin is a new element in the neurogenesis mechanism that may be part of the action of second-generation antipsychotics in the treatment of schizophrenia, indicating more detailed molecular studies are urgently required to fully investigate these potential novel mechanisms of neurogenesis.
SPECT Imaging of SST2-Expressing Tumors with 99mTc-Based Somatostatin Receptor Antagonists: The Role of Tetraamine, HYNIC, and Spacers
Authors: Gaonkar Raghuvir Haridas , Wiesmann Fabius , Del Pozzo Luigi , McDougall Lisa , Zanger Sandra , Mikołajczak Renata , Mansi Rosalba , Fani Melpomeni
Published: March 2021

[99mTc]Tc-HYNIC-TOC is the most widely used 99mTc-labeled somatostatin receptor (SST) agonist for the SPECT imaging of SST-expressing tumors, such as neuroendocrine tumors. Recently, radiolabeled SST antagonists have shown improved diagnostic efficacy over agonists. 99mTc-labeled SST antagonists are lacking in clinical practice. Surprisingly, when [99mTc]Tc-HYNIC was conjugated to the SST2 antagonist SS01, SST2 imaging was not feasible. This was not the case when [99mTc]Tc-N4 was conjugated to SS01. Here, we assessed the introduction of different spacers (X: β-Ala, Ahx, Aun and PEG4) among HYNIC and SS01 with the aim of restoring the affinity of HYNIC conjugates. In addition, we used the alternative antagonist JR11 for determining the suitability of HYNIC with 99mTc-labeled SST2 antagonists. We performed a head-to-head comparison of the N4 conjugates of SS01 and JR11. [99mTc]Tc-HYNIC-TOC was used as a reference, and HEK-SST2 cells were used for in vitro and in vivo evaluation. EDDA was used as a co-ligand for all [99mTc]Tc-HYNIC conjugates. The introduction of Ahx restored, to a great extent, the SST2-mediated cellular uptake of the [99mTc]Tc-HYNIC-X conjugates (X: spacer), albeit lower than the corresponding [99mTc]Tc-N4-conjugates. SPECT/CT images showed that all 99mTc-labeled conjugates accumulated in the tumor and kidneys with [99mTc]Tc-HYNIC-PEG4-SS01, [99mTc]Tc-N4-SS01 and [99mTc]Tc-N4-JR11 having notably higher kidney uptake. Biodistribution studies showed similar or better tumor-to-non-tumor ratios for the [99mTc]Tc-HYNIC-Ahx conjugates, compared to the [99mTc]Tc-N4 counterparts. The [99mTc]Tc-HYNIC-Ahx conjugates of SS01 and JR11 were comparable to [99mTc]Tc-HYNIC-TOC as imaging agents. HYNIC is a suitable chelator for the development of 99mTc-labeled SST2 antagonists when a spacer of appropriate length, such as Ahx, is used.
Addition of Regular Insulin to Ternary Parenteral Nutrition: A Stability Study
Authors: Henry Heloise , Lannoy Damien , Maboudou Patrice , Seguy David , Dine Thierry , Pigny Pascal , Odou Pascal
Published: March 2021

Background: Parenteral nutrition (PN) is a complex medium in which added insulin can become unstable. The aim of this study is, therefore, to evaluate the stability of insulin in PN and to identify influencing factors. Methods: A total of 20 IU/L of regular insulin was added to PN in either glass or Ethylene Vinyl Acetate (EVA) containers. A 24 h stability study was performed via an electrochemiluminescence immunoassay in different media: A ternary PN admixture, separate compartments of the PN bag and a binary admixture. This study was repeated in the absence of zinc, with the addition of serum albumin or tween and with pH adjustment (3.6 or 6.3). Insulin concentration at t time was expressed as a percentage of the initial insulin concentration. Analysis of covariance (ANCOVA) was applied to determine the factors that influence insulin stability. Results: In all PN admixtures, the insulin concentration ratio decreased, stabilising at a 60% and then plateauing after 6 h. At pH 3.6, the ratio was above 90%, while at pH 6.3 it decreased, except in the amino acid solution. ANCOVA (r2 = 0.68, p = 0.01) identified dextrose and pH as significant factors influencing insulin stability. Conclusion: A low pH level seems to stabilise insulin in PN admixtures. The influence of dextrose content suggests that insulin glycation may influence stability.
Alteration of Anticancer and Protein-Binding Properties of Gold(I) Alkynyl by Phenolic Schiff Bases Moieties
Authors: Babgi Bandar A. , Alsayari Jalal , Alenezi Hana M. , Abdellatif Magda H. , Eltayeb Naser E. , Emwas Abdul-Hamid M. , Jaremko Mariusz , Hussien Mostafa A.
Published: March 2021

A set of five gold complexes with the general formula Au(PR3)(C≡C-C6H4-4-R′) (R = PPh3, R′ = –CHO (1), R = PCy3, R′ = –CHO (2), R = PPh3, R′ = –N=CH-C6H4-2-OH (3), R = PPh3, R′ = –N=CH-C6H4-4-OH (4), R = PCy3, R′ = –N=CH-C6H4-2-OH (5)) were synthesized and characterized by elemental analysis, 1H-NMR spectroscopy, 31P-NMR spectroscopy, and mass spectrometry. The structures of complexes 2 and 5 were determined by X-ray crystallography. The effects of the structural modifications on the protein binding affinities and anticancer activities of the five gold complexes were assessed. Fluorescence quenching experiments to assess binding to human serum albumin (HSA) revealed that the Schiff base complexes (3, 4, and 5) had binding constants that were superior to their parent aldehyde complexes and highlighted the position of the hydroxy group because complex 4 (4-hydroxy) had a binding constant 6400 times higher than complex 3 (2-hydroxy). The anticancer activities of the complexes against the OVCAR-3 (ovarian carcinoma) and HOP-62 (non-small-cell lung) cancer cell lines showed that the Schiff bases (3–5) were more cytotoxic than the aldehyde-containing complexes (1 and 2). Notably, compound 4 had cytotoxic activity comparable to that of cisplatin against OVCAR-3, demonstrating the significance of the para position for the hydroxy group. Molecular docking studies against the enzyme thioredoxin reductase (TrxR) and human serum albumin were conducted, with docking scores in good agreement with the experimental data. The current study highlights how small structural modifications can alter physiochemical and anticancer properties. Moreover, this simple design strategy using the aldehyde group can generate extensive opportunities to explore new gold(I)-based anticancer drugs via condensation, cyclization, or nucleophilic addition reactions of the aldehyde.
Enhanced Transport and Permeation of a Polymeric Nanocarrier across the Retina by Mixing with ATP upon Intravitreal Injection
Authors: Kwon Kiyoon , Hwang Youngmin , Jung Junyoung , Tae Giyoong
Published: March 2021

The outer part of the retina pigment epithelium (RPE) in the retina is the main site of neovascularization associated with retinal diseases. However, various obstacles interrupt the delivery of medicines across the RPE, mainly due to the well-developed tight junctions in the RPE. Currently, there is no practical formulation to overcome this issue. In this study, we demonstrated that simple mixing with adenosine tetraphosphate (ATP) has the potential to greatly enhance the transport and permeation of a polymeric nanocarrier across the retina via intravitreal administration. Chitosan-functionalized, pluronic-based nanocarrier (NC), which can deliver various biomolecules efficiently, was used as a polymeric nanocarrier. Mixing with ATP facilitated the diffusion of the nanocarrier in the vitreous humor by reducing the electrostatic interaction between NC and negatively charged glycosaminoglycans (GAGs) in the vitreous humor. Mixing with ATP also allowed the penetration of NC across the whole retina, and it resulted in a great increase (approximately nine times) in the transport of NC across the retina, as well as spreading it throughout the whole retina upon intravitreal administration in a mouse model. This enhanced permeation across the retina was specific to ATP but not to GTP, suggesting the possibility of P2Y receptor-mediated tight junction disruption by ATP.
Systematic Review of l-Arginine for the Treatment of Hypoactive Sexual Desire Disorder and Related Conditions in Women
Authors: Cieri-Hutcherson Nicole E. , Jaenecke Andrea , Bahia Ajeet , Lucas Debra , Oluloro Ann , Stimmel Lora , Hutcherson Timothy C.
Published: March 2021

This systematic review evaluates the efficacy and safety of l-arginine alone or in combination for the treatment of women with hypoactive sexual desire disorder (HSDD) or related conditions, such as female sexual interest/arousal disorder and female sexual arousal disorder. Medline, Embase, International Pharmaceutical Abstracts, Science Direct, and the Cumulative Index to Nursing and Allied Health Literature were searched using keywords “arginine”, “Lady Prelox”, “ArginMax”, “Stronvivo”, “Ristela”, “hypoactive sexual desire disorder”, “female sexual interest arousal disorder”, “female sexual arousal disorder”, “sexual dysfunction”, “sexual behavior”, “dyspareunia”, “libido”, and permutations thereof. Relevant records were retained if they were primary literature, conducted in women with HSDD or related conditions, and published as full text in English. Five randomized controlled trials and two nonrandomized studies met eligibility criteria. Six of the seven studies reported either an increase in the total mean Female Sexual Function Index score or significant increases in multiple domains therein. One study assessed vaginal pulse amplitude and found a statistically significant increase in a combination treatment group compared to placebo. No significant side effects were reported. Four of seven studies had potential risk-of-bias concerns per Cochrane assessments. This systematic review found that combination products containing l-arginine in the form of ArginMax or Lady Prelox may be considered for the treatment of HSDD and related conditions in women regardless of age.
Predisposing, Enabling, and Need Factors Associated with the Choice of Pharmacy Type in the US: Findings from the 2015/2016 National Consumer Survey on the Medication Experience and Pharmacists’ Roles
Authors: Rashrash Mohamed , Sawesi Suhila , Schommer Jon C. , Brown Lawrence M.
Published: March 2021

Background: Knowing the type of pharmacy used by the patient is meaningful to the pharmacist. Previous studies have assessed different factors predicting the kind of pharmacy selection and reached inconsistent findings. Objectives: To identify patient and health-related factors associated with pharmacy type selection. Methods: The Andersen Behavioral Model of Health Service Use was used to organize the selection of patient characteristics and categorize them as predisposing, enabling, and need factors. The dependent variable was the type of pharmacy used. Logistic regression was used to predict the association between patient-related characteristics and the type of pharmacy used. Results: Older age respondents were less likely to use independent pharmacies (OR = 0.992) and more likely to use mail pharmacy services (OR = 1.026). Highly educated people showed higher use of chain and mail pharmacies (OR = 1.272, 1.185, respectively) and less tendency to use the independent, supermarket, and prescription-only pharmacy types. Men were less likely to use chain pharmacies (OR = 0.932) and more likely to use supermarket pharmacies than women. Patients who use Medication Therapy Management (MTM) services had higher odds of using independent and supermarket pharmacies (OR = 2.808, 1.689, respectively). Patients with a higher number of chronic diseases and experienced side effects of medications were more likely to use independent pharmacies (OR for number of disease = 1.097 and for side effects = 1.095). Conclusions: This study’s findings identify characteristics associated with selecting certain pharmacy settings and direct future research to include other predictors encompassing beliefs, attitudes, and other social factors.
Metal and Metalloid Toxicity in Plants: An Overview on Molecular Aspects
Authors: Angulo-Bejarano Paola I. , Puente-Rivera Jonathan , Cruz-Ortega Rocío
Published: March 2021

Worldwide, the effects of metal and metalloid toxicity are increasing, mainly due to anthropogenic causes. Soil contamination ranks among the most important factors, since it affects crop yield, and the metals/metalloids can enter the food chain and undergo biomagnification, having concomitant effects on human health and alterations to the environment. Plants have developed complex mechanisms to overcome these biotic and abiotic stresses during evolution. Metals and metalloids exert several effects on plants generated by elements such as Zn, Cu, Al, Pb, Cd, and As, among others. The main strategies involve hyperaccumulation, tolerance, exclusion, and chelation with organic molecules. Recent studies in the omics era have increased knowledge on the plant genome and transcriptome plasticity to defend against these stimuli. The aim of the present review is to summarize relevant findings on the mechanisms by which plants take up, accumulate, transport, tolerate, and respond to this metal/metalloid stress. We also address some of the potential applications of biotechnology to improve plant tolerance or increase accumulation.
Topical Application of Escherichia coli-Encapsulated dsRNA Induces Resistance in Nicotiana benthamiana to Potato Viruses and Involves RDR6 and Combined Activities of DCL2 and DCL4
Authors: Necira Khouloud , Makki Mongia , Sanz-García Eugenio , Canto Tomás , Djilani-Khouadja Fattouma , Tenllado Francisco
Published: March 2021

Exogenous application of double-stranded RNAs (dsRNAs) for inducing virus resistance in plants represents an attractive alternative to transgene-based silencing approaches. However, improvement of dsRNA stability in natural conditions is required in order to provide long-term protection against the targeted virus. Here, we tested the protective effect of topical application of Escherichia coli-encapsulated dsRNA compared to naked dsRNA against single and dual infection by Potato virus X expressing the green fluorescent protein (PVX-GFP) and Potato virus Y (PVY) in Nicotiana benthamiana. We found that, in our conditions, the effectiveness of E. coli-encapsulated dsRNA in providing RNAi-mediated protection did not differ from that of naked dsRNA. dsRNA vaccination was partly effective against a dual infection by PVX-GFP and PVY, manifested by a delay in the expression of the synergistic symptoms at early times after inoculation. Using PVX-GFP as a reporter virus together with a suite of RNAi knockdown transgenic lines, we have also shown that RNA-directed RNA polymerase 6 and the combined activities of DICER-like 2 (DCL2) and DCL4 act to promote efficient resistance to virus infection conferred by topical application of dsRNA in N. benthamiana. Our results provide evidence that exogenous dsRNA molecules are processed by the RNA silencing pathways commonly used by the host in response to virus infection.
Impact of Mammalian Two-Pore Channel Inhibitors on Long-Distance Electrical Signals in the Characean Macroalga Nitellopsis obtusa and the Early Terrestrial Liverwort Marchantia polymorpha
Authors: Koselski Mateusz , Pupkis Vilmantas , Hashimoto Kenji , Lapeikaite Indre , Hanaka Agnieszka , Wasko Piotr , Plukaite Egle , Kuchitsu Kazuyuki , Kisnieriene Vilma , Trebacz Kazimierz
Published: March 2021

Inhibitors of human two-pore channels (TPC1 and TPC2), i.e., verapamil, tetrandrine, and NED-19, are promising medicines used in treatment of serious diseases. In the present study, the impact of these substances on action potentials (APs) and vacuolar channel activity was examined in the aquatic characean algae Nitellopsis obtusa and in the terrestrial liverwort Marchantia polymorpha. In both plant species, verapamil (20–300 µM) caused reduction of AP amplitudes, indicating impaired Ca2+ transport. In N. obtusa, it depolarized the AP excitation threshold and resting potential and prolonged AP duration. In isolated vacuoles of M. polymorpha, verapamil caused a reduction of the open probability of slow vacuolar SV/TPC channels but had almost no effect on K+ channels in the tonoplast of N. obtusa. In both species, tetrandrine (20–100 µM) evoked a pleiotropic effect: reduction of resting potential and AP amplitudes and prolongation of AP repolarization phases, especially in M. polymorpha, but it did not alter vacuolar SV/TPC activity. NED-19 (75 µM) caused both specific and unspecific effects on N. obtusa APs. In M. polymorpha, NED-19 increased the duration of repolarization. However, no inhibition of SV/TPC channels was observed in Marchantia vacuoles, but an increase in open probability and channel flickering. The results indicate an effect on Ca2+ -permeable channels governing plant excitation.
Efficiency of Herkogamy in Narcissus bulbocodium (Amaryllidaceae)
Authors: Navarro Luis , Ayensa Garbiñe , Sánchez José María
Published: March 2021

Within the theoretical framework of the correlation pleiades, floral phenotypic integration has been proposed as a consequence of selection mediated by pollinators acting on floral characters. Here, we analyzed that assumption by studying the floral biology and pollination of the late-winter species Narcissus bulbocodium L. We found that the flowers of N. bulbocodium are pollinator-dependent (mainly on Bombus terrestris) in terms of achieving optimal levels of seed production (xenogamy mean seed-to-ovule ratio 64%). Flowers are phenotypically integrated, and only the inclusion of the stigma within the corona seems to have a positive and significant influence on the deposition of the pollen. It has been hypothesized that by including the stigma within the corolla, the flower has some control over the contact between stigma and pollinators that could lead to an “ordered herkogamy” as a way to promote outcross and avoid self-interference. Therefore, herkogamy was also studied, and while most previous studies have assessed the evolutionary significance of herkogamy by considering its relationship with outcrossing rates, we approach this phenomenon from a novel direction assessing the relationship between a proxy for herkogamy and the precision of the pollination process. Our results seem to support the existence of an optimal herkogamy distance that could maintain maximum levels of both pollen export and (cross) pollen capture. On the basis of the broad variability of herkogamy that we have found in N. bulbocodium and other data in the literature, we discuss the universality of the adaptive origin of herkogamy.
Potential Role of Nanoparticles in Treating the Accumulation of Amyloid-Beta Peptide in Alzheimer’s Patients
Authors: Abbas Mohamed
Published: March 2021

The disorder of Alzheimer’s is marked by progressive pathophysiological neurodegeneration. The amino acid peptides in the amyloid plaques found in the brains of people with Alzheimer’s disease (AD) are known as amyloid-beta (Aβ). Current treatments are not curative, and the effects associated with AD are reduced. Improving treatment results involved the targeting of drugs at optimum therapeutic concentration. Nanotechnology is seen as an unconventional, modern technology that plays a key role in the treatment of Alzheimer’s disease. Using nanoparticles, molecular detection, effective drug targeting, and their combination offer high sensitivity. The aim of this review is to shed light on the function and successful role of nanoparticles to resolve Aβ aggregation and thus to help cure Alzheimer’s disease. The analysis divides these nanoparticles into three categories: polymer, lipid, and gold nanoparticles. A thorough comparison was then made between the nanoparticles, which are used according to their role, properties, and size in the procedure. The nanoparticles can prevent the accumulation of Aβ during the efficient delivery of the drug to the cells to treat Alzheimer’s disease. Furthermore, this comparison demonstrated the ability of these nanoparticles to deal efficiently with Alzheimer’s disease. The role of these nanoparticles varied from delivering the drug to brain cells to dealing with the disease-causing peptide.
Critical Load Prediction in Notched E/Glass–Epoxy-Laminated Composites Using the Virtual Isotropic Material Concept Combined with the Average Strain Energy Density Criterion
Authors: Sánchez Marcos , Cicero Sergio , Torabi Ali Reza , Ayatollahi Majid Reza
Published: March 2021

This paper attempts to validate the application of the Virtual Isotropic Material Concept (VIMC) in combination with the average strain energy density (ASED) criterion to predict the critical load in notched laminated composites. This methodology was applied to E/glass–epoxy-laminated composites containing U-notches. For this purpose, a series of fracture test data recently published in the literature on specimens with different notch tip radii, lay-up configurations, and a number of plies were employed. It was shown that the VIMC–ASED combined approach provided satisfactory predictions of the last-ply failure (LPF) loads (i.e., critical loads).
Development and Characterization of Rice Husk and Recycled Polypropylene Composite Filaments for 3D Printing
Authors: Morales Maria , Atencio Martinez Cindy , Maranon Alejandro , Hernandez Camilo , Michaud Veronique , Porras Alicia
Published: March 2021

Nowadays the use of natural fiber composites has gained significant interest due to their low density, high availability, and low cost. The present study explores the development of sustainable 3D printing filaments based on rice husk (RH), an agricultural residue, and recycled polypropylene (rPP) and the influence of fiber weight ratio on physical, thermal, mechanical, and morphological properties of 3D printing parts. Thermogravimetric analysis revealed that the composite’s degradation process started earlier than for the neat rPP due to the lignocellulosic fiber components. Mechanical tests showed that tensile strength increased when using a raster angle of 0° than specimens printed at 90°, due to the weaker inter-layer bonding compared to in-layer. Furthermore, inter layer bonding tensile strength was similar for all tested materials. Scanning electron microscope (SEM) images revealed the limited interaction between the untreated fiber and matrix, which led to reduced tensile properties. However, during the printing process, composites presented lower warping than printed neat rPP. Thus, 3D printable ecofriendly natural fiber composite filaments with low density and low cost can be developed and used for 3D printing applications, contributing to reduce the impact of plastic and agricultural waste.