bluuebunny/crossref_metadata_2025 huggingface dataset:
Microalgae as a Source of Valuable Phenolic Compounds and Carotenoids
Authors: Cichoński Jan , Chrzanowski Grzegorz
Published: December 2022

Microalgae are photosynthetic, eukaryotic organisms that are widely used in the industry as cell factories to produce valuable substances, such as fatty acids (polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), sterols (sitosterol), recombinant therapeutic proteins, carbohydrates, vitamins, phenolic compounds (gallic acid, quercetin), and pigments (β-carotene, astaxanthin, lutein). Phenolic compounds and carotenoids, including those extracted from microalgae, possess beneficial bioactivities such as antioxidant capacity, antimicrobial and immunomodulatory activities, and direct health-promoting effects, which may alleviate oxidative stress and age-related diseases, including cardiovascular diseases or diabetes. The production of valuable microalgal metabolites can be modified by using abiotic stressors, such as light, salinity, nutrient availability, and xenobiotics (for instance, phytohormones).
Changes in Gel Characteristics, Rheological Properties, and Water Migration of PSE Meat Myofibrillar Proteins with Different Amounts of Sodium Bicarbonate
Authors: Wu Zhong-Wei , Zou Xiao-Li , Yao Peng-Lei , Kang Zhuang-Li , Ma Han-Jun
Published: December 2022

The changes in the gel and rheological properties and water-holding capacity of PSE meat myofibrillar proteins with different amounts of sodium bicarbonate (SC, 0–0.6/100 g) were studied. Compared to the PSE meat myofibrillar proteins with 0/100 g SC, the texture properties and cooking yield significantly increased (p < 0.05) with increasing SC; meanwhile, adding SC caused the gel color to darken. All samples had similar curves with three phases, and the storage modulus (G’) values significantly increased with the increasing SC. The thermal stability of the PSE meat myofibrillar proteins was enhanced, and the G’ value at 80 °C increased with the increasing SC. Because water was bound more tightly to the protein matrix, the initial relaxation times of T21 and T22 shortened, the peak ratio of P21 significantly increased (p < 0.05), and the P22 significantly decreased (p < 0.05), which implied that the mobility of the water was reduced. Overall, SC could improve the thermal stability of the PSE meat myofibrillar proteins and increase the water-holding capacity and textural properties of the cooked PSE meat myofibrillar protein gels.
Impact of N-Linked Glycosylation on Therapeutic Proteins
Authors: Chen Baoquan , Liu Wenqiang , Li Yaohao , Ma Bo , Shang Shiying , Tan Zhongping
Published: December 2022

Therapeutic proteins have unique advantages over small-molecule drugs in the treatment of various diseases, such as higher target specificity, stronger pharmacological efficacy and relatively low side effects. These advantages make them increasingly valued in drug development and clinical practice. However, although highly valued, the intrinsic limitations in their physical, chemical and pharmacological properties often restrict their wider applications. As one of the most important post-translational modifications, glycosylation has been shown to exert positive effects on many properties of proteins, including molecular stability, and pharmacodynamic and pharmacokinetic characteristics. Glycoengineering, which involves changing the glycosylation patterns of proteins, is therefore expected to be an effective means of overcoming the problems of therapeutic proteins. In this review, we summarize recent efforts and advances in the glycoengineering of erythropoietin and IgG monoclonal antibodies, with the goals of illustrating the importance of this strategy in improving the performance of therapeutic proteins and providing a brief overview of how glycoengineering is applied to protein-based drugs.
Preparation and Optimization of O/W Emulsions Stabilized by Triglycerol Monolaurate for Curcumin Encapsulation
Authors: Zhang Guiqiong , Zhang Qiang , Wang Lan , Ji Lei , Han Pengbing , Zhao Fengju , Su Qun
Published: December 2022

Curcumin is one of the most studied chemo-preventive agents, which may cause suppression, retardation, or inversion of carcinogenesis. But its application is currently limited because of its poor water-solubility and bioaccessibility. A curcumin O/W emulsion was prepared by high-pressure homogenization, using triglyceride monolaurate as an emulsifier and medium chain triglycerides (MCT) as the oil phase. The effects of emulsifiers, emulsifier concentration, oil type, oil-to-water ratio, and homogenization pressure and processing cycles on the physical stability and droplet size distribution of curcumin-encapsulated O/W emulsions were evaluated in this study. The results showed that the mean droplet size of the O/W emulsions remained remarkably stable during 60 days of storage under both light and dark conditions. Curcumin retentions in O/W emulsions after 60 days of storage under light and dark conditions were 97.9% and 81.6%, respectively. In addition, during the simulated gastrointestinal digestion process, the mean droplet size of the O/W emulsions increased from 260 nm to 2743 nm after incubation with simulated gastric fluid (SGF) for 24 h, while the mean droplet size remained unchanged after incubation with simulated intestinal fluid (SIF). The results displayed negligible changes in curcumin content during incubation with simulated gastrointestinal fluids, indicating that effective protection of curcumin was achieved by encapsulation in the O/W emulsion. It is expected that curcumin will acquire high bioaccessibility and bioavailability when the O/W emulsion is to be used in clinical applications.
Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
Authors: Egorov Anton R. , Kurliuk Aleh V. , Rubanik Vasili V. , Kirichuk Anatoly A. , Khubiev Omar , Golubev Roman , Lobanov Nikolai N. , Tskhovrebov Alexander G. , Kritchenkov Andreii S.
Published: December 2022

Ciprofloxacin is one of the most effective antibiotics, but it is characterized by a range of side effects. Elaboration of drug-releasing systems which allow to diminish toxicity of ciprofloxacin is a challenging task in medicinal chemistry. The current study is focused on development of new ciprofloxacin releasing systems (CRS). We found that ultrasound efficiently promotes N,N′-dicyclohexyl carbodiimide-mediated coupling between COOH and NH2 functionalities in water. This was used for conjugation of ciprofloxacin to chitosan. The obtained ciprofloxacin/chitosan conjugates are capable of forming their self-assembled nanoparticles (SANPs) in aqueous medium. The SANPs can be additionally loaded by ciprofloxacin to form new CRS. The CRS demonstrated high loading and encapsulation efficiency and they are characterized by extended release profile (20 h). The elaborated CRS were tested in vivo in rats. The in vivo antibacterial effect of the CRS exceeded that of the starting ciprofloxacin. Moreover, the in vivo acute and subacute toxicity of the nanoparticles was almost identical to that of the chitosan, which is considered as the non-toxic biopolymer.
Fluorescent Pyranoindole Congeners: Synthesis and Photophysical Properties of Pyrano[3,2-f], [2,3-g], [2,3-f], and [2,3-e]Indoles
Authors: Sharapov Ainur D. , Fatykhov Ramil F. , Khalymbadzha Igor A. , Valieva Maria I. , Nikonov Igor L. , Taniya Olga S. , Kopchuk Dmitry S. , Zyryanov Grigory V. , Potapova Anastasya P. , Novikov Alexander S. , Sharutin Vladimir V. , Chupakhin Oleg N.
Published: December 2022

This paper reports the synthesis of four types of annulated pyranoindole congeners: pyrano[3,2-f]indole, pyrano[2,3-g]indole, pyrano[2,3-f]indole, and pyrano[2,3-e]indole and photophysical studies in this series. The synthesis of pyrano[3,2-f], [2,3-g], and [2,3-e]indoles involve a tandem of Bischler–Möhlau reaction of 3-aminophenol with benzoin to form 6-hydroxy- or 4-hydroxyindole followed by Pechmann condensation of these hydroxyindoles with β-ketoesters. Pyrano[2,3-f]indoles were synthesized through the Nenitzescu reaction of p-benzoquinone and ethyl aminocrotonates and subsequent Pechmann condensation of the obtained 5-hydroxyindole derivatives. Among the pyranoindoles studied, the most promising were pyrano[3,2-f] and [2,3-g]indoles. These compounds were characterized by moderate to high quantum yields (30–89%) and a large (9000–15,000 cm−1) Stokes shift. More detailed photophysical studies were carried out for a series of the most promising derivatives of pyrano[3,2-f] and [2,3-g]indoles to demonstrate their positive solvatochromism, and the data collected was analyzed using Lippert-Mataga equation. Quantum chemical calculations were performed to deepen the knowledge of the absorption and emission properties of pyrano[3,2-f] and [2,3-g]indoles as well as to explain their unusual geometries and electronic structures.
The Effects of Iron on In Silico Simulated Abiotic Reaction Networks
Authors: Shahi Sahil Rajiv , Cleaves H. James
Published: December 2022

Iron is one of the most abundant elements in the Universe and Earth’s surfaces, and undergoes a redox change of approximately 0.77 mV in changing between its +2 and +3 states. Many contemporary terrestrial organisms are deeply connected to inorganic geochemistry via exploitation of this redox change, and iron redox reactions and catalysis are known to cause significant changes in the course of complex abiotic reactions. These observations point to the question of whether iron may have steered prebiotic chemistry during the emergence of life. Using kinetically naive in silico reaction modeling we explored the potential effects of iron ions on complex reaction networks of prebiotic interest, namely the formose reaction, the complexifying degradation reaction of pyruvic acid in water, glucose degradation, and the Maillard reaction. We find that iron ions produce significant changes in the connectivity of various known diversity-generating reaction networks of proposed prebiotic significance, generally significantly diversifying novel molecular products by ~20%, but also adding the potential for kinetic effects that could allow iron to steer prebiotic chemistry in marked ways.
Evaluation of the Antioxidant, Cytoprotective and Antityrosinase Effects of Schisandra chinensis Extracts and Their Applicability in Skin Care Product
Authors: Zagórska-Dziok Martyna , Wójciak Magdalena , Ziemlewska Aleksandra , Nizioł-Łukaszewska Zofia , Hoian Uliana , Klimczak Katarzyna , Szczepanek Dariusz , Sowa Ireneusz
Published: December 2022

Plant extracts have been widely used for skin care for many centuries, and nowadays, they are commonly applied for the development and enrichment of new cosmetic preparations. The present study aimed the assessment of the biological activity of aqueous Schisandra chinensis extracts as a potential ingredient of skin care products. The aspects studied involved the ability to neutralize free radicals, impact on viability and metabolism of keratinocytes, as well as tyrosinase inhibitory potential. Our study showed that aqueous S. chinensis extracts have a positive effect on keratinocyte growth and have high antioxidant potential and strong tyrosinase inhibitory activity. UPLC-MS analysis revealed that three groups of phenolic compounds were predominant in the analyzed extract, including lignans, phenolic acids and flavonoids and protocatechiuc and p-coumaryl quinic acids were predominant. Moreover, microwave-assisted extraction, followed by heat reflux extraction, was the most effective for extracting polyphenols. Furthermore, a prototypical natural body washes gel formulation containing the previously prepared extracts was developed. The irritation potential and viscosity were assessed for each of the formulations. The study demonstrated that the addition of these extracts to body wash gel formulations has a positive effect on their quality and may contribute to a decrease in skin irritation. In summary, S. chinensis aqueous extracts can be seen as an innovative ingredient useful in the cosmetic and pharmaceutical industry.
Validation of the Metabolite Ergothioneine as a Forensic Marker in Bloodstains
Authors: Lee Seungyeon , Mun Sora , Lee You-Rim , Lee Jiyeong , Kang Hee-Gyoo
Published: December 2022

Ergothioneine, which is a naturally occurring metabolite, generally accumulates in tissues and cells subjected to oxidative stress, owing to its structural stability at physiological pH; therefore, it has been attracting attention in various biomedical fields. Ergothioneine has also been suggested as a potential forensic marker, but its applicability has not yet been quantitatively validated. In this study, quantitative analysis of ergothioneine in bloodstains was conducted to estimate the age of bloodstains and that of bloodstain donors. Blood from youth and elderly participants was used to generate bloodstains. After extracting metabolites from the bloodstains under prevalent age conditions, ergothioneine levels were quantified by mass spectrometry via multiple reaction monitoring. The concentration of ergothioneine in day 0 bloodstains (fresh blood), was significantly higher in the elderly group than in the youth group, but it did not differ by sex. Statistically significant differences were observed between the samples from the two age groups on days 0, 5 and 7, and on days 2 and 3 compared with day 0. The findings suggest that ergothioneine can be used to estimate the age of bloodstains and of the donor; it could be useful as a potential marker in reconstructing crime scenes.
Rationally Designed Bimetallic Co–Ni Sulfide Microspheres as High-Performance Battery-Type Electrode for Hybrid Supercapacitors
Authors: Rajesh John Anthuvan , Park Jong-Young , Manikandan Ramu , Ahn Kwang-Soon
Published: December 2022

Rational designing of electrode materials is of great interest for improving the performance of battery-type supercapacitors. The bimetallic NiCo2S4 (NCS) and CoNi2S4 (CNS) electrode materials have received much attention for supercapacitors due to their rich electrochemical characteristics. However, the comparative electrochemical performances of NCS and CNS electrodes were never studied for supercapacitor application. In this work, microsphere-like bimetallic NCS and CNS structures were synthesized via a facile one-step hydrothermal method by controlling the molar ratio of Ni and Co precursors. The physico-chemical results confirmed that microsphere-like structures with cubic spinel-type NCS and CNS materials were successfully fabricated by this method. When tested as the supercapacitor electrode materials, both NCS and CNS electrodes exhibited battery-type behavior in a three-electrode configuration with outstanding electrochemical performances such as specific capacity, rate performance and cycle stability. Impressively, the CNS electrode delivered a high specific capacity of 430.1 C g−1 at 1 A g−1, which is higher than 345.9 C g−1 of the NCS electrode. Furthermore, the NCS and CNS electrodes showed a decent cycling stability with 75.70 and 84.70% capacity retention after 10,000 cycles. Benefiting from the electrochemical advantage of CNS microspheres, we fabricated a hybrid supercapacitor (HSC) device based on CNS microspheres (positive electrode) and activated carbon (AC, negative electrode), which is named as CNS//AC. The assembled CNS//AC HSC device showed a large energy density of 41.98 Wh kg−1 at a power density of 800.04 W kg−1 and displayed a remarkable cycling stability with a capacity retention of 91.79% after 15,000 cycles. These excellent electrochemical performances demonstrate that both bimetallic NCS and CNS microspheres may provide potential electrode materials for high performance battery-type supercapacitors.
Variable-Barrier Quantum Coulomb Blockade Effect in Nanoscale Transistors
Authors: Yadav Pooja , Chakraborty Soumya , Moraru Daniel , Samanta Arup
Published: December 2022

Current–voltage characteristics of a quantum dot in double-barrier configuration, as formed in the nanoscale channel of silicon transistors, were analyzed both experimentally and theoretically. Single electron transistors (SET) made in a SOI-FET configuration using silicon quantum dot as well as phosphorus donor quantum dots were experimentally investigated. These devices exhibited a quantum Coulomb blockade phenomenon along with a detectable effect of variable tunnel barriers. To replicate the experimental results, we developed a generalized formalism for the tunnel-barrier dependent quantum Coulomb blockade by modifying the rate-equation approach. We qualitatively replicate the experimental results with numerical calculation using this formalism for two and three energy levels participated in the tunneling transport. The new formalism supports the features of most of the small-scaled SET devices.
Magnetite Nanoparticles as Solar Photo-Fenton Catalysts for the Degradation of the 5-Fluorouracil Cytostatic Drug
Authors: Pérez-Poyatos Lorena T. , Morales-Torres Sergio , Maldonado-Hódar Francisco J. , Pastrana-Martínez Luisa M.
Published: December 2022

Heterogeneous catalysts based on magnetite nanoparticles, Fe3O4, were prepared by the chemical coprecipitation method using iron (III) chloride as a salt precursor. The physicochemical properties of the nanoparticles were determined by different techniques and the efficiency was evaluated for the degradation of the cytostatic drug, 5-fluorouracil (5-FU), in aqueous solution by photo-Fenton process under simulated solar radiation. The most influential parameters, namely pH of the solution, catalyst load, H2O2 dosage, and use of radiation, were studied and optimized in the degradation process. The optimal conditions to achieve a 100% degradation of 5-FU (10 mg L−1) and a high mineralization degree (76%) were established at the acidic pH of 3.0, 100 mg L−1 of catalyst loading, and 58 mM of H2O2 under simulated solar radiation. The contribution of iron leaching to the catalyst deactivation, the role of the dissolved iron ions on homogenous reactions, and the stability of the catalyst were assessed during consecutive reaction cycles.
N-Type Printed Organic Source-Gated Transistors with High Intrinsic Gain
Authors: Hemmi Yudai , Ikeda Yuji , Sporea Radu A. , Takeda Yasunori , Tokito Shizuo , Matsui Hiroyuki
Published: December 2022

Source-gated transistors (SGTs) are emerging devices enabling high-gain single-stage amplifiers with low complexity. To date, the p-type printed organic SGT (OSGT) has been developed and showed high gain and low power consumption. However, complementary OSGT circuits remained impossible because of the lack of n-type OSGTs. Here, we show the first n-type OSGTs, which are printed and have a high intrinsic gain over 40. A Schottky source contact is intentionally formed between an n-type organic semiconductor, poly{[N,N′-bis(2-octyldodecyl)naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′-bithiophene)} (N2200), and the silver electrode. In addition, a blocking layer at the edge of the source electrode plays an important role to improve the saturation characteristics and increase the intrinsic gain. Such n-type printed OSGTs and complementary circuits based on them are promising for flexible and wearable electronic devices such as for physiological and biochemical health monitoring.
Design and Implementation of Graphene-Based Tunable Microwave Filter for THz Applications
Authors: Mutepfe Cleophas D. K. , Srivastava Viranjay M.
Published: December 2022

A reconfigurable Substrate-Integrated Waveguide (SIW) filter operating in the THz region was designed in this work. Two SIW resonators were coupled through a magnetic iris to form a second-order filter with a double-layer substrate. The first substrate was silicon of permittivity 11.9; on top of it, silicon dioxide of permittivity 3.9 was placed. The ground and upper plane were composed of gold plates. Graphene material was then used for the tunability of the filter. A thin graphene sheet was sandwiched between the silicon dioxide substrate and the upper gold plate. An external DC bias voltage was then applied to change the chemical potential of graphene, which, in turn, managed to change the operational center frequency of the filter within the range of 1.289 THz to 1.297 THz, which translated to a bandwidth range of 8 GHz. The second part of this work centered on changing the aspect ratio of the graphene patch to change the center frequency. It was observed that the frequency changed within the range of 1.2908 THz to 1.2929 THz, which gave a bandwidth of 2.1 GHz change.
The Effect of Trunk Position on Attentional Disengagement in Unilateral Spatial Neglect
Authors: Shida Kohei , Amimoto Kazu , Fukata Kazuhiro , Osaki Shinpei , Takahashi Hidetoshi , Makita Shigeru
Published: December 2022

Unilateral spatial neglect (USN) causes difficulties in disengaging attention from the right side to unexpected targets on the left. However, the relationship between egocentric spatial position and attentional disengagement remains unclear. Therefore, this study aimed to clarify the relationship between trunk position and attentional disengagement. Thirty-eight patients with early stroke onset were classified as follows: USN (n = 18), right brain damage without USN (n = 10), and left brain damage (n = 10). The primary outcome was reaction time (RT) in the modified Posner task (MPT). The MPT comprised a condition in which the preceding cue and target direction were the same (valid condition) and a condition in which the directions were opposite (invalid condition). RT to the target was calculated. The MPT was performed in three different trunk positions (trunk midline, left, and right). In each group, the RT was compared on the basis of the stimulus conditions and trunk position. The RT was delayed in the valid and invalid left conditions, especially in the invalid left condition. The RT of the trunk right condition was significantly reduced compared with that of trunk midline and left conditions in the invalid left condition. Thus, trunk position influences attentional disengagement. This study contributes to the rehabilitation of patients with neglect symptoms.
Vitamin D Supplementation Has No Impact on Cardiorespiratory Fitness, but Improves Inflammatory Status in Vitamin D Deficient Young Men Engaged in Resistance Training
Authors: Savolainen Lauri , Timpmann Saima , Mooses Martin , Medijainen Luule , Tõnutare Lisette , Ross Frederik , Lellsaar Märt , Piir Anneli , Zilmer Mihkel , Unt Eve , Ööpik Vahur
Published: December 2022

Data on the effect of vitamin D (Vit-D) supplementation on cardiorespiratory fitness (VO2max) are conflicting. A possible source of discrepancies in the literature is the heterogeneity in baseline Vit-D status among participants in previous studies. The main objectives of the present study were to assess the impact of Vit-D supplementation on VO2max and inflammatory status in Vit-D deficient young healthy men. Participants (n = 39, baseline serum Vit-D level < 50 nmol/L) were quasi-randomly assigned to one of the two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) and concomitantly performed a 12-week supervised resistance training program. During the 12-week intervention, serum Vit-D concentrations increased 3.9-fold (p < 0.001) in the VD group while no changes occurred in the PLC group. Baseline VO2max did not differ in the two groups and remained unchanged during the intervention. Serum interleukin-10/tumour necrosis factor alpha ratio increased significantly (30%, p = 0.007; effect size 0.399) in VD but not in PLC group. In conclusion, 12-week Vit-D supplementation increases serum 25(OH)D levels and improves inflammatory status, but has no impact on VO2max in Vit-D deficient young men engaged in resistance training.
Potential Benefits of Lycopene Consumption: Rationale for Using It as an Adjuvant Treatment for Malaria Patients and in Several Diseases
Authors: Varela Everton , Gomes Antônio , da Silva Barbosa dos Santos Aline , de Carvalho Eliete , Vale Valdicley , Percário Sandro
Published: December 2022

Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. This review aimed to describe the main mechanisms inducing oxidative stress during malaria, highlighting the production of RONS as a defense mechanism against the infection induced by the ischemia-reperfusion syndrome, the metabolism of the parasite, and the metabolism of antimalarial drugs. Furthermore, the effects of lycopene on several diseases in which oxidative stress is implicated as a cause are outlined, providing information about its mechanism of action, and providing an evidence-based justification for its supplementation in malaria.
Prospective Association between Adherence to the Mediterranean Diet and Health-Related Quality of Life in Spanish Children
Authors: Juton Charlotte , Berruezo Paula , Rajmil Luis , Lerin Carles , Fíto Montserrat , Homs Clara , Según Genís , Gómez Santiago F. , Schröder Helmut
Published: December 2022

Health-Related Quality of Life (HRQoL) is gaining attention in children and adolescents because it is an important outcome of their health status and well-being. Therefore, it is important to identify determinants for HRQoL. Currently, there is scarce and mainly cross-sectional evidence on the relationship between adherence to the Mediterranean diet and HRQoL in children and adolescents. Therefore, the objective of the present study was to assess the prospective association between adherence to the Mediterranean diet and HRQoL in Spanish children. The study was carried out in 1371 children aged 8 to 10 from different Catalan elementary schools with a medium follow-up of 15 months. The KidMed and KIDSCREEN-10 questionnaires were used to assess the relationship between diet and HRQoL, respectively. The KidMed score at baseline was positively associated with HRQoL (β = 0.320; 95% CI 0.101–0.540) after adjusting for confounders. Additionally, the logistic regression analysis showed positive associations between baseline consumption of fruit, vegetables, pulses, and high adherence to the Mediterranean diet and HRQoL at follow-up (p < 0.05 for all) while the consumption of fast-food, pasta or rice, baked good or pastries, and sweets were negatively correlated (p < 0.05 for all) with HRQoL at follow-up. In conclusion, adherence of the Mediterranean diet was predictive for HRQoL in Spanish children, but further prospective studies are needed to confirm this result.
Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Biomarkers of Systemic Inflammation: 4-Year Findings from the VITAL Randomized Trial
Authors: Dong Yanbin , Zhu Haidong , Chen Li , Huang Ying , Christen William , Cook Nancy R. , Copeland Trisha , Mora Samia , Buring Julie E. , Lee I-Min , Costenbader Karen H. , Manson JoAnn E.
Published: December 2022

Background: The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study. Objective: To investigate the effects of vitamin D3 and/or n-3 FAs on changes in systemic inflammatory biomarkers including pro- and anti-inflammatory cytokines over a 4-year period in the VITAL sub-cohort with in-person evaluations at the Center for Clinical Investigations (CCI) in Boston. Design: Serum levels of four inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, interleukin-10, and tumor necrosis factor-α) were measured in a total of 2713 samples from those 1054 VITAL/CCI participants (aged 64.9 ± 6.5 years, 49% female, 84% white, and 9% black) at baseline, year 2, and year 4 follow-up visits. Results: In multiple-adjusted models, vitamin D3 supplementation decreased serum hs-CRP levels by 19% at 2-year follow-up (nominal p = 0.007; p-value after multiple comparison adjustment = 0.028), but not at 4-year follow-up (nominal and adjusted p-values > 0.05). The effects of vitamin D3 on other inflammatory markers were not statistically significant either at year 2 or year 4 (all adjusted p-values > 0.05). Marine n-3 FAs were not significantly associated with changes of all the above inflammatory markers either at years 2 and 4, after multiple comparison adjustment (all p-values > 0.05). Conclusions: Vitamin D3 supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, but not other inflammatory biomarkers at year 2 or year 4, while n-3 FAs with or without vitamin D3 did not significantly affect these biomarkers at either time point. Our findings support a potential role of vitamin D supplementation in modulating the chronic inflammatory process, systemic inflammation, and possibly autoimmune disease progression.
Selenium Status: Its Interactions with Dietary Mercury Exposure and Implications in Human Health
Authors: Tinggi Ujang , Perkins Anthony V.
Published: December 2022

Selenium is an essential trace element in humans and animals and its role in selenoprotein and enzyme antioxidant activity is well documented. Food is the principal source of selenium, and it is important that selenium status in the body is adequately maintained for physiological functions. There has been increasing attention on the role of selenium in mitigating the toxic effects of mercury exposure from dietary intake in humans. In contrast, mercury is a neurotoxin, and its continuous exposure can cause adverse health effects in humans. The interactions of selenium and mercury are multi-factorial and involve complex binding mechanisms between these elements at a molecular level. Further insights and understanding in this area may help to evaluate the health implications of dietary mercury exposure and selenium status. This review aims to summarise current information on the interplay of the interactions between selenium and mercury in the body and the protective effect of selenium on at-risk groups in a population who may experience long-term mercury exposure.
Periconceptional Maternal Protein Intake from Animal and Plant Sources and the Impact on Early and Late Prenatal Growth and Birthweight: The Rotterdam Periconceptional Cohort
Authors: van Zundert Sofie , van der Padt Simone , Willemsen Sten , Rousian Melek , Mirzaian Mina , van Schaik Ron , Steegers-Theunissen Régine , van Rossem Lenie
Published: December 2022

Plant-based diets continue to rise in popularity, including among women of reproductive age, while consequences for pregnancy outcomes have hardly been studied. During pregnancy, maternal diet is the only source of proteins for the developing fetus. Hence, we investigated the effects of periconceptional maternal animal and plant protein intake on prenatal growth and birthweight. 501 pregnancies were included from the prospective Rotterdam Periconceptional Cohort. Embryonic growth was depicted by crown-rump length (CRL) and embryonic volume (EV) at 7, 9 and 11 weeks using 3D ultrasound scans. Estimated fetal weight (EFW) at 20 weeks and birthweight were retrieved from medical records and standardized. Multivariable mixed models were used for CRL and EV trajectories, and linear regression for EFW and birthweight. A 10 g/day higher maternal animal protein intake was positively associated with increased embryonic growth (CRL: β = 0.023 √mm, p = 0.052; EV: β = 0.015 ∛cm, p = 0.012). A positive association, albeit non-significant, was found between maternal animal protein intake and EFW, and birthweight. No clear associations emerged between maternal plant protein intake and prenatal growth and birthweight, with effect estimates close to zero. In conclusion, maternal animal protein intake during the periconception period was positively associated with early and late prenatal growth and birthweight, while no associations were found between maternal plant protein intake and prenatal growth and birthweight.
Astragaloside VI Ameliorates Post-Stroke Depression via Upregulating the NRG-1-Mediated MEK/ERK Pathway
Authors: Chen Xi , Shen Jiangang , Zhou Qing , Jin Xinchun , Liu Haosheng , Gao Ran
Published: December 2022

Background: Post-stroke depression (PSD) has been identified as one of the most commonly occurring complications attributed to stroke. Astragaloside VI (AsVI), which is an active Radix Astragali (AR)-derived compound, has been reported to be a potential drug for post-stroke therapy, but its effects on PSD and the underlying mechanisms remain uncovered. Methods: In this study, healthy male SD rats underwent a middle cerebral artery occlusion (MCAO) stroke model. To create a PSD model, these rats were then kept in isolated houses and subjected to chronic unpredictable mild stress. The rats were examined every five days for a series of behavioral tests of depression. The antidepressant properties of AsVI were also investigated in vitro in a corticosterone (CORT)-induced major depression model using a CCK-8 assay. The release of neurotransmitters dopamine (DA)/5-hydroxytryptamine (5-HT) was measured using HPLC. The expression of the neurotrophic factor Neuregulin 1 (NRG-1) in rat brain tissues was detected by immunostaining. The protein expression of NRG-1, p-MEK1, and p-ERK1/2 was analyzed utilizing western blotting. Results: AsVI treatment significantly reduced depression-like behaviors in PSD rats and attenuated the CORT-induced apoptotic cell death in neuronal PC-12 cells. Besides, AsVI treatment remarkably prevented the decrease of the levels of DA and 5-HT in the PSD rat brains and in CORT-induced PC-12 cells. Furthermore, AsVI treatment upregulated the NRG-1-mediated MEK/ERK pathway, which is associated with the improvement of PSD. Conclusions: These findings suggest that AsVI could improve PSD at least partially by upregulating NRG-1-mediated MEK/ERK pathway. AsVI could be a novel therapeutic option for treating PSD.
Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities
Authors: Knak Talea , Abdullaziz Mona A. , Höfmann Stefan , Alves Avelar Leandro A. , Klein Saskia , Martin Matthew , Fischer Markus , Tanaka Nobutada , Kurz Thomas
Published: December 2022

To address the continued rise of multi-drug-resistant microorganisms, the development of novel drugs with new modes of action is urgently required. While humans biosynthesize the essential isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) via the established mevalonate pathway, pathogenic protozoa and certain pathogenic eubacteria use the less well-known methylerythritol phosphate pathway for this purpose. Important pathogens using the MEP pathway are, for example, Plasmodium falciparum, Mycobacterium tuberculosis, Pseudomonas aeruginosa and Escherichia coli. The enzymes of that pathway are targets for antiinfective drugs that are exempt from target-related toxicity. 2C-Methyl-D-erythritol 4-phosphate (MEP), the second enzyme of the non-mevalonate pathway, has been established as the molecular target of fosmidomycin, an antibiotic that has so far failed to be approved as an anti-infective drug. This review describes the development and anti-infective properties of a wide range of fosmidomycin derivatives synthesized over the last four decades. Here we discuss the DXR inhibitor pharmacophore, which comprises a metal-binding group, a phosphate or phosphonate moiety and a connecting linker. Furthermore, non-fosmidomycin-based DXRi, bisubstrate inhibitors and several prodrug concepts are described. A comprehensive structure–activity relationship (SAR) of nearly all inhibitor types is presented and some novel opportunities for further drug development of DXR inhibitors are discussed.
Anti-Alopecia Activity of Alkaloids Group from Noni Fruit against Dihydrotestosterone-Induced Male Rabbits and Its Molecular Mechanism: In Vivo and In Silico Studies
Authors: Susanti Laila , Mustarichie Resmi , Halimah Eli , Kurnia Dikdik , Setiawan Andi , Maladan Yustinus
Published: December 2022

Androgenic alopecia (AA) is a condition that most commonly affects adult men and is caused by an increase in the hormone dihydrotestosterone (DHT) in the hair follicles. Anti-alopecia drugs should be discovered for hair follicles to enter the anagen growth phase. Therefore, this study evaluated the hair growth-promoting activity of Noni fruit’s water, ethyl acetate, n-hexane fractions, and sub-fractions from the active fraction in the alopecia male white rabbit model. The Matias method was modified by inducing rabbits using DHT for 17 days, followed by topical application of Noni fruit solution for 21 days. Meanwhile, hair growth was evaluated by histological observation of the follicular density and the anagen/telogen (A/T) ratio in skin tissue. In the first stage, five groups of male white rabbits were studied to obtain the active fraction; DHT+Minoxidil as standard, DHT+vehicle (NaCMC 1%), DHT+FW, DHT+FEA, and DHT+FH. The FEA as the active fraction was followed by open-column chromatography separation (DCM:Methanol) with a gradient of 10% to produce sub-fractions. In the second stage, the six main sub-fraction groups of male rabbits studied were DHT+FEA-1 to DHT+FEA-6. The follicular density of groups FEA-3 was 78.00 ± 1.52 compared with 31.55 ± 1.64 and 80.12 ± 1.02 in the Vehicle and Minoxidil groups. Additionally, group FEA-3 showed large numbers of anagen follicles with an A/T ratio of 1.64/1 compared to the vehicle group of 1/1.50 and 1.39/1 for Minoxidil control. Group FEA-3 was identified by LC-MS/MS-QTOF, followed by molecular docking to the androgen receptor (PDB: 4K7A), causing alopecia. The results showed that three alkaloid compounds with skeleton piperazine and piperidine, namely (compounds 2 (−4.99 Kcal/mol), 3 (−4.60 Kcal/mol), and 4 (−4.57 Kcal/mol)) had a binding affinity similar to Minoxidil, with also has alkaloid skeleton piperidine–pyrimidine (−4.83 Kcal/mol). The dynamic behavior showed the stability of all androgen receptor compounds with good RMSD, SMSF, and SASA values after being studied with 100 ns molecular dynamics (MD) simulations. This study produced a common thread in discovering a class of alkaloid compounds as inhibitors of androgen receptors that cause alopecia.
Therapeutic Effect of a Latent Form of Cortistatin in Experimental Inflammatory and Fibrotic Disorders
Authors: Campos-Salinas Jenny , Barriga Margarita , Delgado Mario
Published: December 2022

Cortistatin is a cyclic neuropeptide that recently emerged as an attractive therapeutic factor for treating inflammatory, autoimmune, fibrotic, and pain disorders. Despite of its efficiency and apparent safety in experimental preclinical models, its short half-life in body fluids and its potential pleiotropic effects, due to its promiscuity for several receptors expressed in various cells and tissues, represent two major drawbacks for the clinical translation of cortistatin-based therapies. Therefore, the design of new strategies focused on increasing the stability, bioavailability, and target specificity of cortistatin are lately demanded by the industry. Here, we generated by molecular engineering a new cortistatin-based prodrug formulation that includes, beside the bioactive cortistatin, a molecular-shield provided by the latency-associated protein of the transforming growth factor-β1 and a cleavage site specifically recognized by metalloproteinases, which are abundant in inflammatory/fibrotic foci. Using different models of sepsis, inflammatory bowel disease, scleroderma, and pulmonary fibrosis, we demonstrated that this latent form of cortistatin was a highly effective protection against these severe disorders. Noteworthy, from a therapeutic point of view, is that latent cortistatin seems to require significantly lower doses and fewer administrations than naive cortistatin to reach the same efficacy. Finally, the metalloproteinase-cleavage site was essential for the latent molecule to exert its therapeutic action. In summary, latent cortistatin emerges as a promising innovative therapeutic tool for treating chronic diseases of different etiologies with difficult clinical solutions and as a starting point for a rational development of prodrugs based on the use of bioactive peptides.
Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer
Authors: Feng Qiyi , Xiao Kai
Published: December 2022

Lung cancer is a common malignancy worldwide, with high morbidity and mortality. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that not only regulates different hallmarks of cancer, such as tumorigenesis, cell proliferation, and metastasis but also regulates the occurrence and maintenance of cancer stem cells (CSCs). Abnormal STAT3 activity has been found in a variety of cancers, including lung cancer, and its phosphorylation level is associated with a poor prognosis of lung cancer. Therefore, the STAT3 pathway may represent a promising therapeutic target for the treatment of lung cancer. To date, various types of STAT3 inhibitors, including natural compounds, small molecules, and gene-based therapies, have been developed through direct and indirect strategies, although most of them are still in the preclinical or early clinical stages. One of the main obstacles to the development of STAT3 inhibitors is the lack of an effective targeted delivery system to improve their bioavailability and tumor targetability, failing to fully demonstrate their anti-tumor effects. In this review, we will summarize the recent advances in STAT3 targeting strategies, as well as the applications of nanoparticle-mediated targeted delivery of STAT3 inhibitors in the treatment of lung cancer.
A New Synergistic Strategy for Virus and Bacteria Eradication: Towards Universal Disinfectants
Authors: Leclercq Loïc , Nardello-Rataj Véronique
Published: December 2022

In response to the COVID-19 and monkeypox outbreaks, we present the development of a universal disinfectant to avoid the spread of infectious viral diseases through contact with contaminated surfaces. The sanitizer, based on didecyldimethylammonium chloride (DDAC), N,N-bis(3-aminopropyl)dodecylamine (APDA) and γ-cyclodextrin (γ-CD), shows synergistic effects against non-enveloped viruses (poliovirus type 1 and murine norovirus) according to the EN 14476 standard (≥99.99% reduction of virus titer). When a disinfectant product is effective against them, it can be considered that it will be effective against all types of viruses, including enveloped viruses. Consequently, “general virucidal activity” can be claimed. Moreover, we have extended this synergistic action to bacteria (P. aeruginosa, EN 13727). Based on physicochemical investigations, we have proposed two independent mechanisms of action against bacteria and non-enveloped viruses, operating at sub- and super-micellar concentrations, respectively. This synergistic mixture could then be highly helpful as a universal disinfectant to avoid the spread of infectious viral or bacterial diseases in community settings, including COVID-19 and monkeypox (caused by enveloped viruses).
Standardization and Key Aspects of the Development of Whole Yeast Cell Vaccines
Authors: Silva Anna Jéssica Duarte , Rocha Crislaine Kelly da Silva , de Freitas Antonio Carlos
Published: December 2022

In the context of vaccine development, improving antigenic presentation is critical for the activation of specific immune responses and the success of immunization, in addition to selecting an appropriate target. In this sense, different strategies have been developed and improved. Among them is the use of yeast cells as vehicles for the delivery of recombinant antigens. These vaccines, named whole yeast vaccines (WYVs), can induce humoral and cellular immune responses, with the additional advantage of dispensing with the use of adjuvants due to the immunostimulatory properties of their cell wall components. However, there are some gaps in the methodologies for obtaining and validating recombinant strains and vaccine formulations. The standardization of these parameters is an important factor for WYVs approval by regulatory agencies and, consequently, their licensing. This review aimed to provide an overview of the main parameters to consider when developing a yeast-based vaccine, addressing some available tools, and highlighting the main variables that can influence the vaccine production process.
Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of Gold-Nanoparticle-Mediated Radiation Response
Authors: Jackson Nolan , Alhussan Abdulaziz , Bromma Kyle , Jay David , Donnelly James , West Frederick , Lavasanifar Afsaneh , Weinfeld Michael , Beckham Wayne , Chithrani Devika
Published: December 2022

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments.