bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Synthesis and Preliminary Evaluation of the Cytotoxicity and Antibacterial Activity of Novel Triphenylphosphonium Derivatives of Betulin
Authors: Grymel Mirosława , Lalik Anna , Kazek-Kęsik Alicja , Szewczyk Marietta , Grabiec Patrycja , Erfurt Karol
Published: August 2022

For several decades, natural products have been widely researched and their native scaffolds are the basis for the design and synthesis of new potential therapeutic agents. Betulin is an interesting biologically attractive natural parent molecule with a high safety profile and can easily undergo a variety of structural modifications. Herein, we describe the synthesis of new molecular hybrids of betulin via covalent linkage with an alkyltriphenylphosphonium moiety. The proposed strategy enables the preparation of semi-synthetic derivatives (28-TPP⊕ BN and 3,28-bisTPP⊕ BN) from betulin through simple transformations in high yields. The obtained results showed that the presence of a lipophilic cation improved the solubility of the tested analogs compared to betulin, and increased their cytotoxicity. Among the triphenylphosphonium derivatives tested, analogs 7a (IC50 of 5.56 µM) and 7b (IC50 of 5.77 µM) demonstrated the highest cytotoxicity against the colorectal carcinoma cell line (HCT 116). TPP⊕-conjugates with betulin showed antimicrobial properties against Gram-positive reference Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis ATCC 12228 bacteria, at a 200 µM concentration in water. Hence, the conjugation of betulin’s parent backbone with a triphenylphosphonium moiety promotes transport through the hydrophobic barriers of the mitochondrial membrane, making it a promising strategy to improve the bioavailability of natural substances.
Maize Flavonoid Biosynthesis, Regulation, and Human Health Relevance: A Review
Authors: Peniche-Pavía Héctor A. , Guzmán Tereso J. , Magaña-Cerino Jesús M. , Gurrola-Díaz Carmen M. , Tiessen Axel
Published: August 2022

Maize is one of the most important crops for human and animal consumption and contains a chemical arsenal essential for survival: flavonoids. Moreover, flavonoids are well known for their beneficial effects on human health. In this review, we decided to organize the information about maize flavonoids into three sections. In the first section, we include updated information about the enzymatic pathway of maize flavonoids. We describe a total of twenty-one genes for the flavonoid pathway of maize. The first three genes participate in the general phenylpropanoid pathway. Four genes are common biosynthetic early genes for flavonoids, and fourteen are specific genes for the flavonoid subgroups, the anthocyanins, and flavone C-glycosides. The second section explains the tissue accumulation and regulation of flavonoids by environmental factors affecting the expression of the MYB-bHLH-WD40 (MBW) transcriptional complex. The study of transcription factors of the MBW complex is fundamental for understanding how the flavonoid profiles generate a palette of colors in the plant tissues. Finally, we also include an update of the biological activities of C3G, the major maize anthocyanin, including anticancer, antidiabetic, and antioxidant effects, among others. This review intends to disclose and integrate the existing knowledge regarding maize flavonoid pigmentation and its relevance in the human health sector.
Potential Action Mechanism and Inhibition Efficacy of Morinda citrifolia Essential Oil and Octanoic Acid against Stagonosporopsis cucurbitacearum Infestations
Authors: Dalcin Mateus S. , Dias Bruna L. , Viteri Jumbo Luis O. , Oliveira Ana C. S. S. , Araújo Sabrina H. C. , Moura Wellington S. , Mourão Dalmarcia S. C. , Ferreira Talita P. S. , Campos Fabricio S. , Cangussu Alex Sander R. , Alves Marcos V. G. , Andrade Bruno S. , Mantilla-Afanador Javier G. , Aguiar Raimundo W. A. , Oliveira Eugênio E. , Santos Gil R.
Published: August 2022

The use of plant-based products has been shown to efficiently inhibit fungi-mediated diseases in agricultural crops. Here, we extracted and evaluated the composition of noni, Morinda citrifolia L., essential oil and assessed its activities against Stagonosporopsis cucurbitacearum in Cucumis melo L. Using in silico molecular approaches, potential interactions between the essential oil major components and S. cucurbitacearum tyrosine–tRNA ligase were predicted. Finally, we also measured the potential interference of plant physiology (the stomatal conductance and net photosynthesis) mediated by the application of the M. citrifolia essential oil. Chromatographic analysis revealed that octanoic acid (75.8%), hexanoic acid (12.8%), and isobutyl pent-4-enyl carbonate (3.1%) were the major essential oil compounds. Octanoic acid and noni essential oil, when used as preventive measures, reduce fungal mycelial growth at a concentration of 5 mg/mL without causing significant damage to the treated leaves, which reinforces their efficacies as preventive tools against S. cucurbitacearum. Molecular docking analyses predicted very stable interactions between the major essential oil constituents and S. cucurbitacearum tyrosine–tRNA ligase, suggesting the interference of these plant-based molecules upon enzyme activation. Octanoic acid and M. citrifolia essential oil at concentrations of 20 mg/mL decreased the stomatal conductance and net photosynthesis rate of melon plants, resulting in robust phytotoxicity. Collectively, our findings indicated that despite the phytotoxicity risks at higher concentrations, M. citrifolia essential oil and octanoic acid, have potential as alternative tools for the integrative management of S. cucurbitacearum.
Thermodynamic vs. Kinetic Control in Synthesis of O-Donor 2,5-Substituted Furan and 3,5-Substituted Pyrazole from Heteropropargyl Precursor
Authors: Muravev Anton A. , Ovsyannikov Alexander S. , Konorov Gennady V. , Islamov Daut R. , Usachev Konstantin S. , Novikov Alexander S. , Solovieva Svetlana E. , Antipin Igor S.
Published: August 2022

Elaboration of a convenient route towards donor-substituted pyrazoles from heteropropargyl precursors is challenging due to a number of thermodynamically favorable side reactions (e.g., acetylene–allene isomerization and Glaser homocoupling). In this work, Sonogashira cross-coupling conditions of 4-tert-butylphenyl propargyl ether with benzoyl chloride followed by tandem Michael addition/cyclocondensation with hydrazine into 3,5-disubstituted pyrazole (kinetic control), as well as cycloisomerization conditions of ketoacetylene intermediate into 2,5-disubstituted furan (thermodynamic control), were established through a variation of the catalyst loading, solvent polarity, excess of triethylamine, and time of reaction. During the optimization of process parameters, a number of by-products represented by a monophosphine binuclear complex (PPh3PdI2)2 with two bridging iodine atoms and diyne were identified and isolated in the pure form. The quantum-chemical calculations and solution-state 1H/13C NMR spectroscopy suggested that the 5(3)-(4-tert-butylphenyloxy)methoxy-3(5)-phenyl-1H-pyrazole exists in the tautomeric equilibrium in a polar methanol solvent and that individual tautomers could be characterized in case aprotic solvents employed. The pyrazole features a unique tetramer motif in the crystal phase formed by alternating 3(5)-phenyl-1H-pyrazole tautomers, which was stabilized by N–H···N bonds and stacking interactions of pyrazole rings, whereas pyrazole dimers were identified in the gas phase.
Epidermal Growth Factor Receptor Kinase Inhibitor Ameliorates β-Amyloid Oligomer-Induced Alzheimer Disease in Swiss Albino Mice
Authors: Dhamodharan Jagadeesh , Sekhar Ganthimathy , Muthuraman Arunachalam
Published: August 2022

Alzheimer’s disease (AD) is one of the major neurodegenerative disorders, and its incidence increases globally every year. Currently, available AD drugs symptomatically treat AD with multiple adverse effects. Gefitinib (GE) is an epidermal growth factor receptor (EGFR) kinase inhibitor. EGFR is the preferred target for the treatment of AD, whereas the effect of GE in AD conditions is limited. The present study was designed to explore the ameliorative potential of GE in Aβ1–42 oligomer-induced neurotoxicity in AD mice. AD was induced by intracerebroventricular (i.c.v.) injection of Aβ1–42 oligomer (4 μg/4 μL) into the lateral ventricles of the mouse brain. The test compound, i.e., GE (2 and 4 mg/kg of body weight), was administered orally on days 10, 13, 16, 19, 22, 25, and 28, and the reference drug, i.e., donepezil (DP, 2 mg/kg), was administered orally from the 10th to 28th days. The behavioral changes were screened by the Morris water maze (MWM) test. Furthermore, biomarkers i.e., brain acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels were estimated from brain samples. The AD-associated histopathological changes were analyzed by hematoxylin and eosin staining. The administration of GE significantly ameliorated the AD-associated behavioral, biochemical, and histopathological changes. The ameliorative effect of GE against the Aβ1–42 oligomer-associated neurotoxicity was due to its potent inhibition of EGFR kinase activation, as well as its antioxidant and antilipid peroxidative effect.
Phytochemicals and Antioxidant Capacities of Young Citrus Fruits Cultivated in China
Authors: Fang Haitian , Zhang Huiling , Wei Xiaobo , Ye Xingqian , Tian Jinhu
Published: August 2022

Fruits of six varieties of young citrus cultivated in China were collected for phytochemical composition analysis and antioxidant activity determination. The phenolic acids, synephrine, flavone, and flavanone were analyzed using HPLC, and the total phenolic content and antioxidant capacity were determined by Folin-Ciocalteu, Ferric ion reducing antioxidant power (FRAP), 2,2- 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) analysis. The results indicated that Ougan variety had the highest total phenolic content (125.18 GAE mg/g DW), followed by the Huyou variety (107.33 mg/g DW), while Wanshuwenzhoumigan variety had the lowest (35.91 mg/g DW). Ferulic acid was the most dominant soluble phenolic acid in the selected young citrus, followed by p-coumaric acid and p-hydroxybenzoic acid, whereas nobiletin and tangeretin were the most abundant flavones in the Ponkan, Ougan, and Wanshuwenzhoumigan varieties. Antioxidant capacity that measured by ABTS, FRAP, and DPPH showed similar trends and was positively correlated with the total phenolic and total flavonoid contents (p < 0.05). Considering the high content of phenolics in the young fruits of Ougan and Huyou variety, those two varieties might be potential resources for extracting phytochemicals for health promotion.
Biomedical and Textile Applications of Alternanthera sessilis Leaf Extract Mediated Synthesis of Colloidal Silver Nanoparticle
Authors: Kabeerdass Nivedhitha , Murugesan Karthikeyan , Arumugam Natarajan , Almansour Abdulrahman I. , Kumar Raju Suresh , Djearamane Sinouvassane , Kumaravel Ashok Kumar , Velmurugan Palanivel , Mohanavel Vinayagam , Kumar Subbiah Suresh , Vijayanand Selvaraj , Padmanabhan Parasuraman , Gulyás Balázs , Mathanmohun Maghimaa
Published: August 2022

The aqueous extract of Alternanthera sessilis (As) acts as the precursors for the quick reduction of silver ions, which leads to the formation of silver nanoparticles. In the agar, well diffusion method of the Klebsiella pneumoniae shows the minimal inhibitory concentration of 12 mm against A. sessilis mediated silver nanoparticles (As-AgNPs) at 60 µg/mL concentration. Fabric treated with novel AS-AgNPs is tested against the K. pneumoniae and shows an inhibitory action of 12 mm with mixed cotton that determines the antimicrobial efficacy of the fabrics. Uv- visible spectrophotometer was performed, showing a surface plasmon resonance peak at 450 nm cm−1. FTIR shows the vibration and the infrared radiation at a specific wavelength of 500–4000 cm−1. The HR-TEM analysis showed the presence of black-white crystalline, spherical-shaped As-AgNPs embedded on the fabrics range of 15 nm–40 nm. In the scanning electron microscope, the presence of small ball-shaped As-AgNPs embedded on the fabrics at a voltage of 30 KV was found with a magnification of 578X. EDAX was performed in which the nanoparticles show a peak of 2.6–3.9 KeV, and it also reveals the presence of the composition, distribution, and elemental mapping of the nanoparticles. The cytotoxic activity of synthesized nanosilver was carried out against L929 cell lines, which show cell viability at a concentration of 2.5 µg mL−1. Cell proliferation assay shows no cytotoxicity against L929 cell lines for 24 h. In this study, the green synthesis of silver nanoparticles from A. sessilis appears to be a cheap, eco-friendly, and alternative approach for curing infectious ulcers on the floor of the stratum corneum. Nanotechnology conjoined with herbal therapeutics provides a promising solution for wound management.
Engineering Gold Shelled Nanomagnets for Pre-Setting the Operating Temperature for Magnetic Hyperthermia
Authors: Siqueira Elis Regina Lima , Pinheiro Willie Oliveira , Aquino Victor Raul Romero , Coelho Breno Cunha Pinto , Bakuzis Andris Figueiroa , Azevedo Ricardo Bentes , Sousa Marcelo Henrique , Morais Paulo Cesar
Published: August 2022

This study investigated the fabrication of spherical gold shelled maghemite nanoparticles for use in magnetic hyperthermia (MHT) assays. A maghemite core (14 ± 3 nm) was used to fabricate two samples with different gold thicknesses, which presented gold (g)/maghemite (m) content ratios of 0.0376 and 0.0752. The samples were tested in MHT assays (temperature versus time) with varying frequencies (100–650 kHz) and field amplitudes (9–25 mT). The asymptotic temperatures (T∞) of the aqueous suspensions (40 mg Fe/mL) were found to be in the range of 59–77 °C (naked maghemite), 44–58 °C (g/m=0.0376) and 33–51 °C (g/m=0.0752). The MHT data revealed that T∞ could be successful controlled using the gold thickness and cover the range for cell apoptosis, thereby providing a new strategy for the safe use of MHT in practice. The highest SAR (specific absorption rate) value was achieved (75 kW/kg) using the thinner gold shell layer (334 kHz, 17 mT) and was roughly twenty times bigger than the best SAR value that has been reported for similar structures. Moreover, the time that was required to achieve T∞ could be modeled by changing the thermal conductivity of the shell layer and/or the shape/size of the structure. The MHT assays were pioneeringly modeled using a derived equation that was analytically identical to the Box–Lucas method (which was reported as phenomenological).
Current Challenges in Image-Guided Magnetic Hyperthermia Therapy for Liver Cancer
Authors: Sharma Anirudh , Cressman Erik , Attaluri Anilchandra , Kraitchman Dara L. , Ivkov Robert
Published: August 2022

For patients diagnosed with advanced and unresectable hepatocellular carcinoma (HCC), liver transplantation remains the best option to extend life. Challenges with organ supply often preclude liver transplantation, making palliative non-surgical options the default front-line treatments for many patients. Even with imaging guidance, success following treatment remains inconsistent and below expectations, so new approaches are needed. Imaging-guided thermal therapy interventions have emerged as attractive procedures that offer individualized tumor targeting with the potential for the selective targeting of tumor nodules without impairing liver function. Furthermore, imaging-guided thermal therapy with added standard-of-care chemotherapies targeted to the liver tumor can directly reduce the overall dose and limit toxicities commonly seen with systemic administration. Effectiveness of non-ablative thermal therapy (hyperthermia) depends on the achieved thermal dose, defined as time-at-temperature, and leads to molecular dysfunction, cellular disruption, and eventual tissue destruction with vascular collapse. Hyperthermia therapy requires controlled heat transfer to the target either by in situ generation of the energy or its on-target conversion from an external radiative source. Magnetic hyperthermia (MHT) is a nanotechnology-based thermal therapy that exploits energy dissipation (heat) from the forced magnetic hysteresis of a magnetic colloid. MHT with magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs) requires the targeted deposition of MNPs into the tumor, followed by exposure of the region to an AMF. Emerging modalities such as magnetic particle imaging (MPI) offer additional prospects to develop fully integrated (theranostic) systems that are capable of providing diagnostic imaging, treatment planning, therapy execution, and post-treatment follow-up on a single platform. In this review, we focus on recent advances in image-guided MHT applications specific to liver cancer
Passive Deicing CFRP Surfaces Enabled by Super-Hydrophobic Multi-Scale Micro-Nano Structures Fabricated via Femtosecond Laser Direct Writing
Authors: Zhang Zihan , Zhou Jiakang , Ren Yuqi , Li Weihan , Li Sheng , Chai Nianyao , Zeng Zhongle , Chen Xiangyu , Yue Yunfan , Zhou Ling , Cheng Yibing , Li Shuxin , Wang Xuewen
Published: August 2022

Carbon fiber reinforced plastic (CFRP) is the main material of aircraft skin. Preparing superhydrophobic anti-icing/deicing surface on the CFRP is of great importance for aircraft flight safety. In this work, a variety of multi-scale micro-nano structures were imprinted on CFRP by femtosecond laser processing, and a transition from hydrophilic to superhydrophobic CFRP was realized. After being optimized by different geometries and laser conditions, the water contact angle, which is tested at 24.3 °C and 34% humidity, increased from 88 ± 2° (pristine) to 149 ± 3° (100 μm groove) and 153 ± 3° (80 μm grid). A further anti-icing test at −10 °C (measured on the cooling platform) and 28% humidity showed that the freezing time was increased from 78 ± 10 s (pristine) to 282 ± 25 s (80 μm grid). Most importantly, the tensile tests showed that the femtosecond laser processing method did not deteriorate the mechanical properties of CFRP. This work provides great significance for aircraft passive deicing technology.
Synthesis and Characterization of Coordination Compound [Eu(µ2-OC2H5)(btfa)(NO3)(phen)]2phen with High Luminescence Efficiency
Authors: Culeac Ion P. , Verlan Victor I. , Bordian Olga T. , Zubareva Vera E. , Iovu Mihail S. , Bulhac Ion I. , Siminel Nichita A. , Siminel Anatolii V. , Mihai Geanina , Enachescu Marius
Published: August 2022

A high-luminescent, blue-light excitable europium(III) coordination complex, [Eu(µ2-OC2H5)(btfa)(NO3)(phen)]2phen (1) {btfa = benzoyl trifluoroacetone, phen = 1,10-phenantroline}, has been synthesized and investigated. The complex was characterized by infrared (IR) and photoluminescence (PL) spectroscopy. The PL emission spectra of powder samples registered in a range of 10.7–300 K exhibit characteristic metal-centered luminescence bands, assigned to internal radiative transitions of the Eu3+ ion, 5D1→7Fj and 5D0→7Fj (j = 0–4). The high-resolution spectrum of the transition 5D0→7F0 shows that it consists of two narrow components, separated by 0.96 meV, which indicates the presence in the matrix of two different sites of the Eu3+ ion. The splitting pattern of 5D0→7Fj (j = 0–4) transitions indicates that europium ions are located in a low-symmetry environment. The absolute quantum yield and the sensitization efficiency were determined to be 49.2% and 89.3%, respectively. The complex can be excited with low-cost lasers at around 405 nm and is attractive for potential applications in optoelectronics and biochemistry.
Inverse Association between Dietary Diversity Score Calculated from the Diet Quality Questionnaire and Psychological Stress in Chinese Adults: A Prospective Study from China Health and Nutrition Survey
Authors: Zhou Jia , Wang Huan , Zou Zhiyong
Published: August 2022

Specific nutrients or dietary patterns influence an individual’s psychological stress. As a major aspect of a healthy diet, the influence of dietary diversity on psychological stress remains uncertain. Within these contexts, we aimed to examine the association between the dietary diversity score and psychological stress, using prospective data from the China Health and Nutrition Survey (CHNS). We included 7434 adult participants, with complete dietary information, in the 2011 wave, and followed-up with perceived stress scale (PSS-14) in the 2015 wave. The dietary intake of foods was coded into 29 food groups, using the DQQ for China, and the dietary diversity scores were obtained, using DQQ, by calculating the number of food groups consumed during one 24-h dietary recall. The univariate analysis, and logistic regression model were used to examine the relationship between psychological stress and diet diversity. Approximately half of the participants (4204, 56.55%) perceived a higher level of stress (PSS-14 total score > 25). Dietary diversity was lower in the higher-stress group (p for trend <0.0001). Unconditional multivariate logistic regression demonstrated that participants with higher daily dietary diversity were less likely to experience higher-level psychological stress, compared with participants with lower daily dietary diversity (ORs range: 0.480–0.809). Dietary diversity was found to be inversely associated with psychological stress, in this prospective analysis of a national population. Further studies are required to figure out the mechanism and effectiveness of dietary diversity on psychological stress.
Maternal Docosahexaenoic Acid Exposure Needed to Achieve Maternal–Newborn EQ
Authors: Christifano Danielle N. , Gustafson Kathleen M. , Carlson Susan E. , Sultanna Nasrin , Brown Alexandra , Sands Scott A. , Colombo John , Gajewski Byron J.
Published: August 2022

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant’s DHA status at delivery is known as maternal–newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants (n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study.
Cinnamaldehyde and Curcumin Prime Akt2 for Insulin-Stimulated Activation
Authors: Urasaki Yasuyo , Le Thuc T.
Published: August 2022

In this study, the effects of cinnamaldehyde and curcumin on Akt2, a serine/threonine protein kinase central to the insulin signaling pathway, were examined in preadipocytes. Cinnamaldehyde or curcumin treatment increased Akt2 phosphorylation at multiple sites including T450 and Y475, but had no effect on Akt2 phosphorylation at S474, which is critical for Akt2 activation. Surprisingly, insulin treatment with cinnamaldehyde or curcumin increased p-Akt2 (S474) by 3.5-fold versus insulin treatment alone. Furthermore, combined cinnamaldehyde, curcumin, and insulin treatment increased p-Akt2 (S474) by 7-fold versus insulin treatment alone. Interestingly, cinnamaldehyde and curcumin inhibited both serine/threonine phosphatase 2A (PP2A) and protein tyrosine phosphatase 1B (PTP1B). Akt2 activation is a multistep process that requires phosphorylation at T450 for proper folding and maturation, and phosphorylation of both Y475 and S474 for stabilization of the catalytic domain. It is plausible that by inhibiting PP2A and PTP1B, cinnamaldehyde and curcumin increase phosphorylation at T450 and Y475, and prime Akt2 for insulin-stimulated phosphorylation at S474. Notably, the combination of a PP2A inhibitor, okadaic acid, and a PTP1B inhibitor increased p-Akt2 (S474), even in the absence of insulin. Future combinations of PP2A and PTP1B inhibitors provide a rational platform to engineer new therapeutics for insulin resistance syndrome.
Effect of Dietary Phosphorous Restriction on Fibroblast Growth 2 Factor-23 and sKlotho Levels in Patients with Stages 1–2 Chronic Kidney Disease
Authors: Saxena Anita , Sachan Trisha , Gupta Amit , Kapoor Vishwas
Published: August 2022

Hyperphosphatemia has emerged as an independent risk factor for cardiovascular disease (CVD) and excess mortality in chronic kidney disease (CKD). The study evaluates the effect of dietary phosphorus (Ph) restriction (DPhR) at an early stage as a therapeutic strategy for delaying CKD progression and preventing CVD. Methods: This was a one-year interventional study conducted on 79 stage 1 and 2 CKD patients. The dietary phosphorus intake (DPhI), fibroblast growth factor-23 (FGF-23), sKlotho and serum phosphorous (SP) levels were analyzed. Patients were categorized into two groups based on their DPhI, recommended DPhI (RPhI) with <1000 mg/day of dietary phosphorous (dietary counselling) and high DPhI (HPhI) with >1000 mg/day (dietary intervention). For comparisons of differences between the two groups, independent t-test; for correlation analysis, Pearson correlation; for identifying the significant associated risk factors for CKD, binary logistic regression analysis and for comparing the means across the three visits, repeated measures ANOVA were used for statistical analysis. Results: The mean age and glomerular filtration rate (GFR) of CKD patients were 38 ± 12 years and 82.95 ± 16.93 mL/min/1.73 m2. FGF-23, SP, dietary protein and DPhI were significantly higher and sKlotho was significantly lower in HPhI group than RPhI group. In HPhI group; GFR, sKlotho, SP and FGF-23 correlated significantly with DPhI. Risk factors with a statistical bearing on the progression of CKD were animal-based diet, family history of CKD and hypertension. In HPhI group; GFR, DPhI, SP and FGF-23 levels significantly improved within the intervention period whereas a significant increase in sKlotho levels was observed in both the groups. Conclusion: Restricting DPhI emerged as a favorable therapeutic strategy for CKD patients for improving renal function and controlling hyperphosphatemia. The results of the present study may serve as the basis for future interventional studies with dietary phosphate restriction in the initial stages of CKD that would preserve renal function. Highlights: Early restriction of dietary phosphorus prevents decline in eGFR, elevation in FGF23 and increases Klotho levels.
Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer
Authors: Grenville Zoe S. , Noor Urwah , His Mathilde , Viallon Vivian , Rinaldi Sabina , Aglago Elom K. , Amiano Pilar , Brunkwall Louise , Chirlaque María Dolores , Drake Isabel , Eichelmann Fabian , Freisling Heinz , Grioni Sara , Heath Alicia K. , Kaaks Rudolf , Katzke Verena , Mayén-Chacon Ana-Lucia , Milani Lorenzo , Moreno-Iribas Conchi , Pala Valeria , Olsen Anja , Sánchez Maria-Jose , Schulze Matthias B. , Tjønneland Anne , Tsilidis Konstantinos K. , Weiderpass Elisabete , Winkvist Anna , Zamora-Ros Raul , Key Timothy J. , Smith-Byrne Karl , Travis Ruth C. , Schmidt Julie A.
Published: August 2022

Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.
Probiotic Lactiplantibacillus plantarum Tana Isolated from an International Weightlifter Enhances Exercise Performance and Promotes Antifatigue Effects in Mice
Authors: Lee Mon-Chien , Chen Ming-Ju , Huang Hsiao-Wen , Wu Wei-Kai , Lee Yi-Wei , Kuo Hsing-Chun , Huang Chi-Chang
Published: August 2022

Exercise causes changes in the gut microbiota, and in turn, the composition of the gut microbiota affects exercise performance. In addition, the supplementation of probiotics is one of the most direct ways to change the gut microbiota. In recent years, the development and application of human-origin probiotics has gradually attracted attention. Therefore, we obtained intestinal Lactiplantibacillus plantarum “Tana” from a gold-medal-winning weightlifter, who has taken part in various international competitions such as the World Championships and the Olympic Games, to investigate the benefits of Tana supplementation for improving exercise performance and promoting antifatigue effects in mice. A total of 40 male Institute of Cancer Research (ICR) mice were divided into four groups (10 mice/group): (1) vehicle (0 CFU/mice/day), (2) Tana-1× (6.15 × 107 CFU/mice/day), (3) Tana-2× (1.23 × 108 CFU /mice/day), and (4) Tana-5× (3.09 × 108 CFU/mice/day). After four weeks of Tana supplementation, we found that the grip strength, endurance exercise performance, and glycogen storage in the liver and muscle were significantly improved compared to those in the vehicle group (p < 0.05). In addition, supplementation with Tana had significant effects on fatigue-related biochemical markers; lactate, ammonia, and blood urea nitrogen (BUN) levels and creatine kinase (CK) activity were significantly lowered (p < 0.05). We also found that the improved exercise performance and antifatigue benefits were significantly dose-dependent on increasing doses of Tana supplementation (p < 0.05), which increased the abundance and ratio of beneficial bacteria in the gut. Taken together, Tana supplementation for four weeks was effective in improving the gut microbiota, thereby enhancing exercise performance, and had antifatigue effects. Furthermore, supplementation did not cause any physiological or histopathological damage.
Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa
Authors: Vonaesch Pascale , Winkel Munir , Kapel Nathalie , Nestoret Alison , Barbot-Trystram Laurence , Pontoizeau Clément , Barouki Robert , Rakotondrainipiana Maheninasy , Kandou Kaleb , Andriamanantena Zo , Andrianonimiadana Lova , Habib Azimdine , Rodriguez-Pozo Andre , Hasan Milena , Vigan-Womas Inès , Collard Jean-Marc , Gody Jean-Chrysostome , Djorie Serge , Sansonetti Philippe J. , Randremanana Rindra Vatosoa ,   on behalf of the Afribiota Investigators
Published: August 2022

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2–5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.
Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms
Authors: Lu Mong-Liang , Ku Wei-Chi , Syifa Nailis , Hu Shu-Chin , Chou Chia-Te , Wu Yi-Hsio , Kuo Po-Hsiu , Chen Chun-Hsin , Chen Wei J. , Wu Tzu-Hua
Published: August 2022

Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC–MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 μL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.
Development of Spatial Orientation in Two-to-Three-Year-Old Children in Relation to Lifestyle Factors
Authors: van Dun Claudia , Lisi Ilaria , van Diepen Janna , Gross Gabriele , Janzen Gabriele , Aarts Esther
Published: August 2022

Various lifestyle factors, including diet, physical activity, and sleep, have been studied in the context of children’s health. However, how these lifestyle factors contribute to the development of cognitive abilities, including spatial cognition, remains vastly understudied. One landmark in spatial cognitive development occurs between 2.5 and 3 years of age. For spatial orientation at that age, children learn to use allocentric reference frames (using spatial relations between objects as the primary reference frame) in addition to, the already acquired, egocentric reference frames (using one’s own body as the primary reference frame). In the current virtual reality study in a sample of 30–36-month-old toddlers (N = 57), we first demonstrated a marginally significant developmental shift in spatial orientation. Specifically, task performance with allocentric performance increased relative to egocentric performance (ηp2 = 0.06). Next, we explored a variety of lifestyle factors, including diet, in relation to task performance, to explain individual differences. Screen time and gestational weight gain of the mother were negatively associated with spatial task performance. The findings presented here can be used to guide future confirmatory studies about the role of lifestyle factors in the development of spatial cognition.
The Validity and Reliability of the FANTASTIC Questionnaire for Nutritional and Lifestyle Studies in University Students
Authors: Murillo-Llorente María Teresa , Brito-Gallego Renata , Alcalá-Dávalos María Luisa , Legidos-García María Ester , Pérez-Murillo Javier , Perez-Bermejo Marcelino
Published: August 2022

The FANTASTIC questionnaire is a scientific instrument that can be used by health professionals for quickly and effectively measuring the quality of life and lifestyle of people. It is a simple questionnaire that measures different dimensions including nutritional status, but the possibility of using it as a resource for studies in the nutritional field (regardless of its correlation with this) has never been considered, nor has it been used for studies in university populations. The aim was to validate the FANTASTIC questionnaire to report on the participant’s lifestyle in a Spanish university population by using a cross-sectional study. A sample of 501 participants was obtained. The study was approved by the Ethics Research Committee of Catholic University of Valencia, and written informed consent was obtained from all participants. Sociodemographic, lifestyle variables, habitual diet, and nutrition-related lifestyle were collected individually. Participants also completed the self-administered FANTASTIC questionnaire. The reliability analysis of the FANTASTIC questionnaire revealed a Cronbach’s Alpha statistic result of 0.797. The Kaiser–Meyer–Olkin (KMO) value was 0.786, with a significant Bartlett’s Test of Sphericity (p = 0.000). This shows that the FANTASTIC questionnaire has good internal consistency and good construct validity. A retest was performed in four weeks’ time, showing excellent intraclass correlation values. We consider the applicability of the FANTASTIC questionnaire for nutritional studies in Spanish university students to be appropriate, and most students have high scores in the nutritional aspects of the questionnaire, showing correct diet implementation and good cooking skills.
Vitamin D3 Repletion Improves Vascular Function, as Measured by Cardiorenal Biomarkers in a High-Risk African American Cohort
Authors: Sinha Satyesh K. , Sun Ling , Didero Michelle , Martins David , Norris Keith C. , Lee Jae Eun , Meng Yuan-Xiang , Sung Jung Hye , Sayre Michael , Carpio Maria Beatriz , Nicholas Susanne B.
Published: August 2022

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.
Overgrowth of Squamocolumnar Junction and Dysregulation of Stem Cell Lineages in the Stomach of Vitamin A-Deficient Mice
Authors: Vins Neethu , Sugathan Subi , Al Menhali Asma , Karam Sherif M.
Published: August 2022

Junctional epithelia are common sites for pathological transformations. In mice, the stratified epithelium of the forestomach joins the simple glandular epithelium of the cardia at the limiting ridge. We previously demonstrated the expression of vitamin A receptors in the gastric stem/progenitor cells and their progeny and found that excess retinoic acid enhances cellular dynamics of gastric epithelium. This study examines how deficiency of vitamin A would alter gastric epithelial stem cell lineages. Three-week-old mice of both genders were weaned and fed with a vitamin A deficient (VAD) diet for 4 or 8 months. Sex- and weight-matched littermate mice received a standard (control) diet. To label S-phase cells, all mice received a single intraperitoneal injection of 5-bromo-2-deoxyuridine before being euthanized. Stomach tissues were processed for microscopic examination and protein analysis to investigate stem cell lineages using different stains, lectins, or antibodies. The Student’s t-test was used to compare quantified data showing differences between control and VAD groups. Eight-month-vitamin-A deficiency caused enlarged forestomach and overgrowth of the squamocolumnar junction with metaplastic and dysplastic cardiac glands, formation of intramucosal cysts, loss of surface mucosal integrity, increased amount of luminal surface mucus, and upregulation of trefoil factor 1 and H+,K+-ATPase. These changes were associated with decreased cell proliferation and upregulation of p63. In conclusion, vitamin A is necessary for maintaining gastric epithelial integrity and its deficiency predisposes the mouse stomach to precancerous lesions.
The N-terminal Subunit of the Porcine Deltacoronavirus Spike Recombinant Protein (S1) Does Not Serologically Cross-react with Other Porcine Coronaviruses
Authors: Yen Lu , Magtoto Ronaldo , Mora-Díaz Juan Carlos , Carrillo-Ávila Jose Antonio , Zhang Jianqiang , Cheng Ting-Yu , Magtoto Precy , Nelli Rahul K. , Baum David H. , Zimmerman Jeffrey J. , Giménez-Lirola Luis G.
Published: August 2022

Porcine deltacoronavirus (PDCoV), belonging to family Coronaviridae and genus Deltacoronavirus, is a major enteric pathogen in swine. Accurate PDCoV diagnosis relying on laboratory testing and antibody detection is an important approach. This study evaluated the potential of the receptor-binding subunit of the PDCoV spike protein (S1), generated using a mammalian expression system, for specific antibody detection via indirect enzyme-linked immunosorbent assay (ELISA). Serum samples were collected at day post-inoculation (DPI) −7 to 42, from pigs (n = 83) experimentally inoculated with different porcine coronaviruses (PorCoV). The diagnostic sensitivity of the PDCoV S1-based ELISA was evaluated using serum samples (n = 72) from PDCoV-inoculated animals. The diagnostic specificity and potential cross-reactivity of the assay was evaluated on PorCoV-negative samples (n = 345) and samples collected from pigs experimentally inoculated with other PorCoVs (n = 472). The overall diagnostic performance, time of detection, and detection rate over time varied across different S/P cut-offs, estimated by Receiver Operating Characteristic (ROC) curve analysis. The higher detection rate in the PDCoV group was observed after DPI 21. An S/P cut-off of 0.25 provided 100% specificity with no serological cross-reactivity against other PorCoV. These results support the use of S1 protein-based ELISA for accurate detection of PDCoV infections, transference of maternal antibodies, or active surveillance.
Effectiveness of Household Disinfection Techniques to Remove SARS-CoV-2 from Cloth Masks
Authors: Mares-Guia Maria Angélica Monteiro Mello , Paiva Anne Aline Pereira , Mello Vinicius Motta , Eller Cristiane M. , Salvio Andreza Lemos , Nascimento Felipe F. , Silva Emanuelle S. R. F. , Campos Vinicius Tadeu Martins Guerra , da Silva Mendes Ygara , Lemos Elba Regina Sampaio , Sousa Ivanildo P. , Horta Marco Aurélio Pereira
Published: August 2022

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, and viral RNA was extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, such as soap powder (1.60 × 104, 1.04 × 103), soap powder and Lysoform® (1.60 × 104, 1.04 × 103), and alcohol 70% (1.02 × 103, 5.91 × 101), respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction in the number of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51,759, p < 0.05). In conclusion, the role of sodium hypochlorite in cloth mask disinfection may also have implications for future health emergencies as well as recommendation by WHO.
Optimized 68Ga-Labeled Urea-Based PSMA-Targeted PET Tracers for Prostate Cancer
Authors: Wu Yitian , Zhang Xiaojun , Zhang Ying , Xu Baixuan , Tian Jiahe , Zhang Jinming
Published: August 2022

Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have become some of the most promising tools for the diagnosis and therapy prostate cancer (PCa). The structure of existing PSMA-targeted PET tracers still needs to be optimized to improve their pharmacokinetic properties and tumor-to-background ratio. In this study, we modified the structure of a well-studied PSMA tracer, and six novel tracers with variable hydrophilicity and pharmacokinetics were developed and evaluated both in vitro and in vivo. All of the novel tracers showed high hydrophilicity (log p = −2.99 ± 0.33 to −3.49 ± 0.01), rapid clearance rates (elimination half-times = 15.55 to 35.97 min), and high affinity for PSMA (Ki = 8.11 ± 0.49 to 42.40 ± 2.11 nM) in vitro. Specific cell binding and micro-PET experiments showed that [68Ga]Ga-PSMA-Q displayed the highest specific PSMA+ cell uptake (3.75 ± 0.35 IA%/106 at 60 min), tumor uptake (SUVmax = 0.97 ± 0.24 at 60 min p.i.), and tumor-to-muscle ratio (59.33 ± 5.72 at 60 min p.i.), while the tumor-to-muscle ratio was much higher than that of [68Ga]Ga-PSMA-617. The results of this study validate the clinical potential of [68Ga]Ga-PSMA-Q for PET imaging and further targeted therapy of prostate cancer.