bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-Fermentation of Glucose–Xylose Mixtures from Agroindustrial Residues by Ethanologenic Escherichia coli: A Study on the Lack of Carbon Catabolite Repression in Strain MS04
Authors: Sierra-Ibarra Estefanía , Vargas-Tah Alejandra , Moss-Acosta Cessna L. , Trujillo-Martínez Berenice , Molina-Vázquez Eliseo R. , Rosas-Aburto Alberto , Valdivia-López Ángeles , Hernández-Luna Martín G. , Vivaldo-Lima Eduardo , Martínez Alfredo
Published: December 2022

The production of biofuels, such as bioethanol from lignocellulosic biomass, is an important task within the sustainable energy concept. Understanding the metabolism of ethanologenic microorganisms for the consumption of sugar mixtures contained in lignocellulosic hydrolysates could allow the improvement of the fermentation process. In this study, the ethanologenic strain Escherichia coli MS04 was used to ferment hydrolysates from five different lignocellulosic agroindustrial wastes, which contained different glucose and xylose concentrations. The volumetric rates of glucose and xylose consumption and ethanol production depend on the initial concentration of glucose and xylose, concentrations of inhibitors, and the positive effect of acetate in the fermentation to ethanol. Ethanol yields above 80% and productivities up to 1.85 gEtOH/Lh were obtained. Furthermore, in all evaluations, a simultaneous co-consumption of glucose and xylose was observed. The effect of deleting the xyIR regulator was studied, concluding that it plays an important role in the metabolism of monosaccharides and in xylose consumption. Moreover, the importance of acetate was confirmed for the ethanologenic strain, showing the positive effect of acetate on the co-consumption rates of glucose and xylose in cultivation media and hydrolysates containing sugar mixtures.
Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review
Authors: Muhammad Aliyu , Forcados Gilead Ebiegberi , Yusuf Abdurrahman Pharmacy , Abubakar Murtala Bello , Sadiq Idris Zubairu , Elhussin Isra , Siddique Md. Abu Talha , Aminu Suleiman , Suleiman Rabiatu Bako , Abubakar Yakubu Saddeeq , Katsayal Babangida Sanusi , Yates Clayton C. , Mahavadi Sunila
Published: December 2022

For many patients, diabetes Mellitus and Malignancy are frequently encountered comorbidities. Diabetes affects approximately 10.5% of the global population, while malignancy accounts for 29.4 million cases each year. These troubling statistics indicate that current treatment approaches for these diseases are insufficient. Alternative therapeutic strategies that consider unique signaling pathways in diabetic and malignancy patients could provide improved therapeutic outcomes. The G-protein-coupled estrogen receptor (GPER) is receiving attention for its role in disease pathogenesis and treatment outcomes. This review aims to critically examine GPER’ s comparative role in diabetes mellitus and malignancy, identify research gaps that need to be filled, and highlight GPER’s potential as a therapeutic target for diabetes and malignancy management. There is a scarcity of data on GPER expression patterns in diabetic models; however, for diabetes mellitus, altered expression of transport and signaling proteins has been linked to GPER signaling. In contrast, GPER expression in various malignancy types appears to be complex and debatable at the moment. Current data show inconclusive patterns of GPER expression in various malignancies, with some indicating upregulation and others demonstrating downregulation. Further research should be conducted to investigate GPER expression patterns and their relationship with signaling pathways in diabetes mellitus and various malignancies. We conclude that GPER has therapeutic potential for chronic diseases such as diabetes mellitus and malignancy.
Cell-Penetrating Peptide–Peptide Nucleic Acid Conjugates as a Tool for Protein Functional Elucidation in the Native Bacterium
Authors: Yokoi Yasuhito , Kawabuchi Yugo , Zulmajdi Abdullah Adham , Tanaka Reiji , Shibata Toshiyuki , Muraoka Takahiro , Mori Tetsushi
Published: December 2022

Approximately 30% or more of the total proteins annotated from sequenced bacteria genomes are annotated as hypothetical or uncharacterized proteins. However, elucidation on the function of these proteins is hindered by the lack of simple and rapid screening methods, particularly with novel or hard-to-transform bacteria. In this report, we employed cell-penetrating peptide (CPP) –peptide nucleotide acid (PNA) conjugates to elucidate the function of such uncharacterized proteins in vivo within the native bacterium. Paenibacillus, a hard-to-transform bacterial genus, was used as a model. Two hypothetical genes showing amino acid sequence similarity to ι-carrageenases, termed cgiA and cgiB, were identified from the draft genome of Paenibacillus sp. strain YYML68, and CPP–PNA probes targeting the mRNA of the acyl carrier protein gene, acpP, and the two ι-carrageenase candidate genes were synthesized. Upon direct incubation of CPP–PNA targeting the mRNA of the acpP gene, we successfully observed growth inhibition of strain YYML68 in a concentration-dependent manner. Similarly, both the function of the candidate ι-carrageenases were also inhibited using our CPP–PNA probes allowing for the confirmation and characterization of these hypothetical proteins. In summary, we believe that CPP–PNA conjugates can serve as a simple and efficient alternative approach to characterize proteins in the native bacterium.
Adhesion and Anti-Adhesion Abilities of Potentially Probiotic Lactic Acid Bacteria and Biofilm Eradication of Honeybee (Apis mellifera L.) Pathogens
Authors: Leska Aleksandra , Nowak Adriana , Czarnecka-Chrebelska Karolina Henryka
Published: December 2022

Lactic acid bacteria (LAB) naturally inhabits the organisms of honeybees and can exhibit adhesive properties that protect these insects against various pathogenic microorganisms. Thus, cell surface (auto-aggregation, co-aggregation, hydrophobicity) and adhesive properties of LAB to two abiotic (polystyrene and glass) and four biotic (collagen, gelatin, mucus, and intestinal Caco-2 cells) surfaces were investigated. Additionally, anti-adhesion activity and the eradication of honeybee pathogen biofilms by LAB metabolites (culture supernatants) were determined. The highest hydrophobicity was demonstrated by Pediococcus pentosaceus 19/1 (63.16%) and auto-aggregation by Lactiplantibacillus plantarum 18/1 (71.91%). All LAB showed a broad spectrum of adhesion to the tested surfaces. The strongest adhesion was noted for glass. The ability to co-aggregate with pathogens was tested for the three most potently adherent LAB strains. All showed various levels of co-aggregation depending on the pathogen. The eradication of mature pathogen biofilms by LAB metabolites appeared to be weaker than their anti-adhesive properties against pathogens. The most potent anti-adhesion activity was observed for L. plantarum 18/1 (98.80%) against Paenibacillus apiarius DSM 5582, while the strongest biofilm eradication was demonstrated by the same LAB strain against Melissococcus plutonius DSM 29964 (19.87%). The adhesive and anti-adhesive activity demonstrated by LAB can contribute to increasing the viability of honeybee colonies and improving the conditions in apiaries.
Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease
Authors: Lazarev Vladimir F. , Dutysheva Elizaveta A. , Mikhaylova Elena R. , Trestsova Maria A. , Utepova Irina A. , Chupakhin Oleg N. , Margulis Boris A. , Guzhova Irina V.
Published: December 2022

The risk of progression of most sporadic neurodegenerative diseases, including Alzheimer’s disease, increases with age. Traditionally, this is associated with a decrease in the efficiency of cell protection systems, in particular, molecular chaperones. Thus, the development of small molecules able to induce the synthesis of chaperones is a promising therapeutic approach to prevent neural diseases associated with ageing. Here, we describe a new compound IA-50, belonging to the class of indolylazines and featured by a low size of topological polar surface area, the property related to substances with potentially high membrane-penetrating activity. We also estimated the absorption, distribution, metabolism and excretion characteristics of IA-50 and found the substance to fit the effective drug criteria. The new compound was found to induce the synthesis and accumulation of Hsp70 in normal and aged neurons and in the hippocampi of young and old mice. The transgenic model of Alzheimer’s disease, based on 5xFAD mice, confirmed that the injection of IA-50 prevented the formation of β-amyloid aggregates, loss of hippocampal neurons and the development of memory impairment. These data indicate that this novel substance may induce the expression of chaperones in neural cells and brain tissues, suggesting its possible application in the therapy of ageing-associated disorders.
Crystallization and Structural Properties of Oleogel-Based Margarine
Authors: Chai Xiuhang , Zhang Yujin , Shi Yifei , Liu Yuanfa
Published: December 2022

Interest in oleogel as a promising alternative to traditional hydrogenated vegetable oil has increasingly grown in recent years due to its low content of saturated fatty acids and zero trans fatty acids. This study aimed to develop wax-based margarine to replace traditional commercial margarine. The wax-based margarine was prepared and compared with commercial margarine in texture, rheology, and microscopic morphology. The possibility of preparing margarine at room temperature (non-quenched) was also explored. The results showed that the hardness of oleogel-based margarine increased as the BW concentration increased. Denser droplets and crystal network structure were observed with the increase in BW content. XRD patterns of oleogel-based margarine with different content BW were quite similar and structurally to the β′ form. However, the melting temperature of oleogel-based margarine was over 40 °C at each concentration, which represented a poor mouth-melting characteristic. In addition, the unique, improved physical properties of oleogel-based margarine were obtained with binary mixtures of China lacquer wax (ZLW) and Beeswax (BW), due to the interaction of the ZLW and BW crystal network. The rapid cooling process improved the spreadability of oleogel-based margarine. The margarine prepared by 5% BW50:ZLW50 had similar properties to commercial margarine in texture and melting characteristics (37 °C), which had the potential to replace commercial margarine.
In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein
Authors: Basnet Saroj , Marahatha Rishab , Shrestha Asmita , Bhattarai Salyan , Katuwal Saurav , Sharma Khaga Raj , Marasini Bishnu P. , Dahal Salik Ram , Basnyat Ram Chandra , Patching Simon G. , Parajuli Niranjan
Published: December 2022

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia—a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal—using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2.
Synthesis of Aliphatic Polycarbonates from Diphenyl Carbonate and Diols over Zinc (II) Acetylacetonate
Authors: Feng Jun , Li Jin , Feng Jian , Wei Zhong , Wang Ziqing , Song Xiaoling
Published: December 2022

APCs (aliphatic polycarbonates) are one of the most important types of biodegradable polymers and widely used in the fields of solid electrolyte, biological medicine and biodegradable plastics. Zinc-based catalysts have the advantages of being low cost, being non-toxic, having high activity, and having excellent environmental and biological compatibility. Zinc (II) acetylacetonate (Zn(Acac)2) was first reported as a highly effective catalyst for the melt transesterification of biphenyl carbonate with 1,4-butanediol to synthesize poly(1,4-butylene carbonate)(PBC). It was found that the weight-average molecular weight of PBC derived from Zn(Acac)2 could achieve 143,500 g/mol with a yield of 85.6% under suitable reaction conditions. The Lewis acidity and steric hindrance of Zn2+ could obviously affect the catalytic performance of Zn-based catalysts for this reaction. The main reasons for the Zn(Acac)2 catalyst displaying a higher yield and Mw than other zinc-based catalysts should be ascribed to the presence of the interaction between acetylacetone ligand and Zn2+, which can provide this melt transesterification reaction with the appropriate Lewis acidity as well as the steric hindrance.
Effects of Fermented Citrus Peel on Ameliorating Obesity in Rats Fed with High-Fat Diet
Authors: Huang Chung-Hsiung , Hsiao Shun-Yuan , Lin Yung-Hsiang , Tsai Guo-Jane
Published: December 2022

Although citrus peel is a waste material, it contains a variety of bioactive components. As our preliminary findings showed that citrus peels fermented with Saccharomyces cerevisiae T1 contained increased levels of anti-obesity flavonoids, the objective of this study was to prepare fermented citrus peel and to investigate its effect on ameliorating obesity in Sprague Dawley (SD) rats fed with a high-fat diet (HFD). After fermentation, the amounts of limonene, nobiletin and 3-methoxynobiletin in citrus peel were markedly increased. SD rats were fed with an HFD for 10 weeks, followed by fermented citrus peel-containing HFD (0.3% or 0.9% w/w) for 6 weeks. Compared with those fed with an HFD alone, lower levels of body weight, visceral fat, body fat percentage, blood triglyceride, total cholesterol, low-density lipoprotein, malondialdehyde and hepatic adipose accumulation were observed in rats fed with fermented citrus peel. In parallel, hepatic levels of acetyl-CoA carboxylase and fatty acid synthase were diminished, and the level of hormone sensitivity lipase in visceral fat was elevated. These results reveal fermented citrus peel is a promising natural product with beneficial effects of alleviating HFD-induced obesity.
Development of a Proton-Enhanced ESI UPLC-MS/MS Method for the Determination of Tetrodotoxin
Authors: Li Tong , Wang Ruiguo , Wang Peilong
Published: December 2022

Tetrodotoxin (TTX) is a kind of low-molecular-weight non-protein neurotoxin. It is one of the most potent neurotoxins found in nature, and it is found in puffer fish and various marine biota. The low sensitivity of previous analytical methods limited their application in puffer fish organ samples. This study established a method for the accurate and fast determination of TTX by reversed ultra-performance liquid chromatography coupled with proton-enhanced electron spray ionization–tandem mass spectrometry. The method yields good peak shapes, high sensitivity and low coeluted interferences. The method was successfully applied to determine TTX in puffer fish tissue samples of about 0.2 g.
Ultraviolet-Sensitive Properties of Graphene Nanofriction
Authors: Dong Gaolong , Ding Shuyang , Peng Yitian
Published: December 2022

The friction characteristics of two-dimensional materials in the ultraviolet (UV) radiation environment are important to the reliability of two-dimensional material nano-structures of space equipment. A novel mechanism of UV light-sensitive nano-friction on graphene was proposed by ultraviolet vacuum irradiation modification using an atomic force microscope (AFM). The surface roughness, adhesion force, and friction of graphene were gradually reduced over a time of irradiation below 3 min. UV185 passes through graphene and causes photochemical reactions between its bottom layer and Si/SiO2 substrate, resulting in hydroxyl, carboxyl, and silanol suspension bonds and sp3-like bonds, which enhances the binding energy of graphene on the substrate and inhibits the out-of-plane deformation resulting in roughness and friction reduction. However, as the irradiation time increased to 5 min, the friction force increased rapidly with the aging effect and the breakdown of sp3-like bonds between the graphene–substrate interface. This study presents a new method of controlling nanofriction on graphene based on UV irradiation-sensitive posterities in vacuum conditions, which is essential to the application of two-dimensional materials in aerospace equipment, to improve anti-aging properties and wear reduction.
Optimized High-Content Imaging Screening Quantifying Micronuclei Formation in Polymer-Treated HaCaT Keratinocytes
Authors: Saadati Fariba , da Silva Brito Walison Augusto , Emmert Steffen , Bekeschus Sander
Published: December 2022

Research on nano- and micro-plastic particles (NMPPs) suggests their potential threat to human health. Some studies have even suggested genotoxic effects of NMPP exposure, such as micronuclei (MN) formation, while others found the opposite. To clarify the ability of NMPP to induce MN formation, we used non-malignant HaCaT keratinocytes and exposed these to a variety of polystyrene (PS) and poly methyl methacrylate (PMMA) particle types at different concentrations and three different sizes. Investigations were performed following acute (one day) and chronic exposure (five weeks) against cytotoxic (amino-modified NMPPs) and genotoxic (methyl methanesulfonate, MMS) positive controls. An optimized high-content imaging workflow was established strictly according to OECD guidelines for analysis. Algorithm-based object segmentation and MN identification led to computer-driven, unsupervised quantitative image analysis results on MN frequencies among the different conditions and thousands of cells per condition. This could only be realized using accutase, allowing for partial cell detachment for optimal identification of bi-nucleated cells. Cytotoxic amino-modified particles were not genotoxic; MMS was both. During acute and long-term studies, PS and PMMA particles were neither toxic nor increased MN formation, except for 1000 nm PS particles at the highest concentration of unphysiological 100 µg/mL. Interestingly, ROS formation was significantly decreased in this condition. Hence, most non-charged polymer particles were neither toxic nor genotoxic, while aminated particles were toxic but not genotoxic. Altogether, we present an optimized quantitative imaging workflow applied to a timely research question in environmental toxicity.
Manufacturing of Carbon Nanotube-Polystyrene Filament for 3D Printing: Nanoparticle Dispersion and Electromagnetic Properties
Authors: Baskakova Kseniya I. , Okotrub Alexander V. , Bulusheva Lyubov G. , Sedelnikova Olga V.
Published: December 2022

3D printing is a promising technology for creating polymer objects of a given architecture with specified functional properties. In fact, the choice of filaments for 3D printing is quite limited. Here, we report a process for producing polystyrene filaments with 0.0025–2 wt.% single-walled carbon nanotubes (SWCNTs) by extruding crushed polystyrene composites. The resulting filaments are characterized by a high uniformity of filler distribution and the absence of air pores. Comparison of microscopy data and electromagnetic properties of base composites and composite materials printed from filaments showed that extrusion and printing improve SWCNT dispersion. The proposed method can be used to create filaments for 3D printing of objects from various base polymers containing functional fillers up to the electrical percolation threshold and above.
Fresh-Cut Eruca Sativa Treated with Plasma Activated Water (PAW): Evaluation of Antioxidant Capacity, Polyphenolic Profile and Redox Status in Caco2 Cells
Authors: Ramazzina Ileana , Lolli Veronica , Lacey Karen , Tappi Silvia , Rocculi Pietro , Rinaldi Massimiliano
Published: December 2022

Plasma Activated Water (PAW) has recently emerged as a promising non-chemical and non-thermal technology for the microbial decontamination of food. However, its use as a replacement for conventional disinfection solutions needs further investigation, as the impact of reactive species generated by PAW on nutritional food quality, toxicology, and safety is still unclear. The purpose of this study is to investigate how treatment with PAW affects the health-promoting properties of fresh-cut rocket salad (Eruca sativa). Therefore, the polyphenolic profile and antioxidant activity were evaluated by a combination of UHPLC-MS/MS and in vitro assays. Moreover, the effects of polyphenolic extracts on cell viability and oxidative status in Caco2 cells were assessed. PAW caused a slight reduction in the radical scavenging activity of the amphiphilic fraction over time but produced a positive effect on the total phenolic content, of about 70% in PAW-20, and an increase in the relative percentage (about 44–50%) of glucosinolate. Interestingly, the PAW polyphenol extract did not cause any cytotoxic effect and caused a lower imbalance in the redox status compared to an untreated sample. The obtained results support the use of PAW technology for fresh-cut vegetables to preserve their nutritional properties.
Association between Diet Quality and Index of Non-Alcoholic Steatohepatitis in a Large Population of People with Type 2 Diabetes: Data from the TOSCA.IT Study
Authors: Vitale Marilena , Della Pepa Giuseppe , Costabile Giuseppina , Bozzetto Lutgarda , Cipriano Paola , Signorini Stefano , Leoni Valerio , Riccardi Gabriele , Vaccaro Olga , Masulli Maria
Published: December 2022

Background: There are still open questions with respect to the optimal dietary treatment in patients with type 2 diabetes (T2D) and coexisting non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate, in patients with T2D, the association between NASH, dietary component intake, food groups and adherence to the Mediterranean diet. Methods: Cross-sectional analysis of 2026 people with T2D (1136 men and 890 women). The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. NASH was identified by the Index Of NASH (ION). Based on the cluster analysis two dietary patterns were identified: the NASH and the NO-NASH pattern. Results: The macronutrient composition of the diet was similar in the two patterns. However, the NASH pattern compared with the NO-NASH pattern was characterized by a significantly lower content of fibre (p < 0.001), β-carotene (p < 0.001), vitamin C (p < 0.001), vitamin E (p < 0.001), polyphenols (p = 0.026) and antioxidant capacity (p < 0.001). With regard to food consumption, the NASH pattern compared with NO-NASH pattern was characterized by higher intake of rice (p = 0.021), potatoes (p = 0.013), red (p = 0.004) and processed meat (p = 0.003), and a lower intake of wholegrain bread (p = 0.019), legumes and nuts (p = 0.049), vegetables (p = 0.047), fruits (p = 0.002), white meat (p = 0.001), fatty fish (p = 0.005), milk and yogurt (p < 0.001). Conclusions: NO-NASH dietary pattern was characterized by a food consumption close to the Mediterranean dietary model, resulting in a higher content of polyphenols, vitamins, and fibre. These finding highlight the potential for dietary components in the prevention/treatment of NASH in people with T2D.
Oxidized Dietary Oil, High in Omega-3 and Omega-6 Polyunsaturated Fatty Acids, Induces Antioxidant Responses in a Human Intestinal HT29 Cell Line
Authors: Østbye Tone-Kari Knutsdatter , Haugen John-Erik , Wetterhus Elin Merete , Bergum Silje Kristine , Nilsson Astrid
Published: December 2022

When oxidized, dietary oils generate products which have the potential to cause adverse effects on human health. The objective of the study was to investigate whether lipid oxidation products in an oxidized dietary oil can be taken up in intestinal cells, induce antioxidant stress responses and potentially be harmful. The in vitro cell model HT29 was exposed to camelina oil with different extents of oxidation, or only 4-hydroxy-2-hexenal (HHE) or 4-hydroxy-2-nonenal (HNE). The cellular content of HHE increased with an increasing extent of oxidation of the camelina oil added to the cell’s growth media, whereas HNE did not show a similar trend. Deuterated HHE was taken up by the HT29 cells, with 140 µM HHE metabolized within 0.5–1 h. The low oxidation degree of the camelina oil increased the gene expression of antioxidant markers (GPX, ATF6, XBP1). The increase in the gene expression of SOD at medium oxidation levels of the oil might indicate different regulation mechanisms. Highly oxidized camelina oil and a low concentration of HHE, over time, induced SOD and catalase enzyme activity in HT29 cells. Oxidized camelina oil contains multiple oxidation products which can be responsible for the intracellular responses observed in HT29 cells, while HHE and HNE in combination with other oxidation products induce antioxidant defence responses.
Prevalence and Implications of Low Reticulocyte–Hemoglobin Levels among Extreme Preterm Neonates: A Single-Center Retrospective Study
Authors: Sriranjan Jhanahan , Kalata Christine , Fusch Gerhard , Thomas Karen , Goswami Ipsita
Published: December 2022

This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with neurodevelopmental outcomes at 18–24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and December 2019, who received routine iron supplementation were enrolled. Iron deficiency was defined as reticulocyte–hemoglobin (Ret-Hb) levels ≤ 29 pg at 36 weeks corrected age. A subcohort of neonates completed standardized developmental assessment at 18–24 months corrected age. Significant neurodevelopmental impairment (sNDI) was defined as either Bayley Scales of Infant Development score < 70 or cerebral palsy or blindness or hearing aided. Among a cohort of 215 neonates [GA 25.8 (1.7) weeks, birthweight 885 (232) g], prevalence of iron deficiency was 55%, 21%, 26%, and 13%, in neonates <24 weeks, 24–25 + 6 weeks, 26–27 + 6 weeks, and ≥ 28 weeks GA, respectively. Male sex and receipt of corticosteroid therapy were associated with iron-deficiency. In the subcohort analysis (n = 69), there was no statistically significant association between Ret-Hb levels at 36 weeks corrected age and the risk of sNDI [OR 0.99 (95% CI 0.85–1.2)]. Male infants and those who received postnatal corticosteroids are likely to have iron-limited erythropoiesis at corrected term despite routine iron-supplementation; however, low Ret-Hb levels during the neonatal period were not associated with significant neurological disability in early childhood.
Ideal Cardiovascular Health Metrics Are Associated with Reduced Severity of Hepatic Steatosis and Liver Fibrosis Detected by Transient Elastography
Authors: Fan Heze , Xu Chenbo , Li Wenyuan , Huang Yuzhi , Hua Rui , Xiong Ying , Yang Yuxuan , Feng Xueying , Wang Zihao , Yuan Zuyi , Zhou Juan
Published: December 2022

Life’s Simple 7 (LS7) is the American Heart Association’s (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. We performed a cross-sectional study using the data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) cycle. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate the severity of hepatic steatosis and liver fibrosis and to define NAFLD, advanced liver fibrosis, and cirrhosis. A total of 2679 participants were included. Multivariate linear regression analysis revealed that per 1-unit increase in the CVH metric, CAP and LSM decreased by 8.565 units and 0.274 units, respectively. In the multivariate logistic regression analysis, the risk of NAFLD, advanced liver fibrosis, and cirrhosis were 7, 10, and 6 times higher in the poor CVH group than in the ideal CVH group. Subgroup analysis indicated that CVD patients and non-Hispanic whites could benefit more from ideal CVH. In conclusion, adherence to ideal CVH metrics, as proposed by the AHA, can significantly reduce the risk of hepatic steatosis and liver fibrosis.
Drops of Capillary Blood Are Not Appropriate for Hemoglobin Measurement with Point-of-Care Devices: A Comparative Study Using Drop Capillary, Pooled Capillary, and Venous Blood Samples
Authors: De la Cruz-Góngora Vanessa , Méndez-Gómez-Humarán Ignacio , Gaona-Pineda Elsa Berenice , Shamah-Levy Teresa , Dary Omar
Published: December 2022

Population-based surveys matched by time but using different methodologies for determining hemoglobin (Hb) concentration have shown inconsistencies in estimating anemia prevalence. This study aimed to estimate measurement errors in Hb quantification in HemoCue 201+ using venous blood (VB) and capillary blood both drops (DCB) and pools (PCB), and compare the results against those of a reference method (VB analyzed in hematology analyzers based on the cyanmethemoglobin method). Children (n = 49), adult females (n = 50), and older adults (n = 50) were randomly allocated to donate VB (4 mL) and either DCB (three drops) or PCB (350 µL). Results in HemoCue were analyzed through Bland Altman and Lyn’s concordance against Hb concentration by the reference method. A positive average bias (systematic error) was found for the HemoCue (0.31 g/dL) using the same VB samples. This value was then subtracted from all readings carried out in the device. After this adjustment, DCB still produced a positive bias (0.42 ± 0.81 g/dL), and the variation of single results was ±1.6 g/dL (95% CI). PCB and VB performed similarly; the average bias was negligible (−0.02 ± 0.36 and 0.00 ± 0.33 g/dL, respectively) and the variation of the results (95% CI) was ±0.7 g/dL or lower. Lyn’s concordance values were 0.86, 0.96, and 0.98 for DCB, PCB, and VB, respectively. Random variation using DCB is too large to approximate the true Hb values, and therefore DCB should be discontinued for diagnosing anemia both in individuals and in populations.
Comparative Pharmacokinetic of Curcuminoids Formulations with an Omega-3 Fatty Acids Monoglyceride Carrier: A Randomized Cross-Over Triple-Blind Study
Authors: Aguilera Ester Cisneros , Vachon Annick , Plourde Mélanie
Published: December 2022

There is a growing interest for curcuminoids in the general population and the scientific research community. Curcuminoids, derived from turmeric spice, are lipophiles and therefore have a low solubility in water which hence have a low bioavailability in the human plasma. To circumvent this issue, a natural product developed by Biodroga Nutraceuticals combined curcuminoids with omega-3 fatty acids (OM3) esterified in monoglycerides (MAG). The objective was to perform a 24 h pharmacokinetics in humans receiving a single dose of curcuminoid formulated by three different means, and to compare their plasma curcuminoids concentration. Sixteen males and fifteen females tested three formulations: 400 mg of curcuminoids powder extract, 400 mg of curcuminoids in rice oil and 400 mg of curcuminoids with 1 g MAG-OM3. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 h post dose intake. Plasma samples were analyzed by ultra high-performance liquid chromatography with a triple quadrupole mass spectrometer (UPLC-MS/MS). Twenty-four hours after a single dose intake, the total plasma curcuminoids area under the curve (AUC) reached 166.8 ± 17.8 ng/mL*h, 134.0 ± 12.7 ng/mL*h and 163.1 ± 15.3 ng/mL*h when curcuminoids were provided with MAG-OM3, with rice oil or in powder, respectively. The Cmax of total curcuminoids reached between 11.9–17.7 ng/mL at around 4 h (Tmax). One-hour post-dose, the curcuminoids plasma concentration was 40% higher in participants consuming the MAG-OM3 compared to the other formulations. Thus, in a young population, plasma curcuminoids 24 h pharmacokinetics and its increase shortly after the single dose intake were higher when provided with MAG-OM3 than rice oil.
Kreon® (Creon®) vs. Lipancrea®: In Vitro Comparison of Two Encapsulated Pancreatin Preparations
Authors: Hartmann Sven , Rydzewska Grazyna , Domínguez-Muñoz J. Enrique
Published: December 2022

Kreon® (Creon®) and Lipancrea® are pancreatic enzyme supplements indicated in the treatment of exocrine pancreatic insufficiency. In order to determine their interchangeability, an in vitro comparison of their physical properties and enzymatic activity was carried out. Capsule fill weight and particle size were also determined in order to establish their physical properties. Amylase, lipase and protease activities, lipase release at different pHs and the dissolution time of pellets were assessed for enzymatic analysis. The length range of Kreon® and Lipancrea® pellets was 1.1–2.2 mm and 1.5–2.8 mm, respectively. Protease activity was below the label claim for Lipancrea® and above for Kreon® presentations. Lipase and amylase activity were equal to or higher than the label claim in both preparations. In dissolution experiments simulating the stomach passage, significant release of lipase activity was observed for Lipancrea® (% actual activity: 41% for Lipancrea® 8000; 21% for Lipancrea® 16000) after 60 min at pH 5.0. No release of lipase activity was observed for Kreon® at that particular pH. Enzyme release for Lipancrea® at pH 6.0 was generally slower than for Kreon® and seemed to be influenced by the preceding incubation at lower pH. More than 85% of Kreon® and Lipancrea® dissolved in a pH 6.0 phosphate buffer within 20 min. Despite the similarities of the enzyme content on the respective labels, Kreon® and Lipancrea® differ in pellet size, enzymatic activity and release. This may impact their therapeutic efficacy and, therefore, may limit their interchangeability.
Native Study of the Behaviour of Magnetite Nanoparticles for Hyperthermia Treatment during the Initial Moments of Intravenous Administration
Authors: Marassi Valentina , Zanoni Ilaria , Ortelli Simona , Giordani Stefano , Reschiglian Pierluigi , Roda Barbara , Zattoni Andrea , Ravagli Costanza , Cappiello Laura , Baldi Giovanni , Costa Anna L. , Blosi Magda
Published: December 2022

Magnetic nanoparticles (MNPs) present outstanding properties making them suitable as therapeutic agents for hyperthermia treatments. Since the main safety concerns of MNPs are represented by their inherent instability in a biological medium, strategies to both achieve long-term stability and monitor hazardous MNP degradation are needed. We combined a dynamic approach relying on flow field flow fractionation (FFF)-multidetection with conventional techniques to explore frame-by-frame changes of MNPs injected in simulated biological medium, hypothesize the interaction mechanism they are subject to when surrounded by a saline, protein-rich environment, and understand their behaviour at the most critical point of intravenous administration. In the first moments of MNPs administration in the patient, MNPs change their surrounding from a favorable to an unfavorable medium, i.e., a complex biological fluid such as blood; the particles evolve from a synthetic identity to a biological identity, a transition that needs to be carefully monitored. The dynamic approach presented herein represents an optimal alternative to conventional batch techniques that can monitor only size, shape, surface charge, and aggregation phenomena as an averaged information, given that they cannot resolve different populations present in the sample and cannot give accurate information about the evolution or temporary instability of MNPs. The designed FFF method equipped with a multidetection system enabled the separation of the particle populations providing selective information on their morphological evolution and on nanoparticle–proteins interaction in the very first steps of infusion. Results showed that in a dynamic biological setting and following interaction with serum albumin, PP-MNPs retain their colloidal properties, supporting their safety profile for intravenous administration.
Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches
Authors: Hmingthansanga Victor , Singh Nidhi , Banerjee Superna , Manickam Sivakumar , Velayutham Ravichandiran , Natesan Subramanian
Published: December 2022

The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin’s stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach. Surmounting the significant barrier properties of the skin in a well-organised, momentary, and harmless approach is still challenging. Chemical permeation enhancers (CPEs) with higher activity are associated with certain side effects restricting their advancement in transdermal drug delivery. Furthermore, complexity in the interaction of CPEs with the skin has led to difficulty in elucidating the mechanism of action. Nevertheless, CPEs-aided transdermal drug delivery will accomplish its full potential due to advancements in analytical techniques, synthetic chemistry, and combinatorial studies. This review focused on techniques such as drug–vehicle interaction, vesicles and their analogues, and novel CPEs such as lipid synthesis inhibitors (LSIs), cell-penetrating peptides (CPPs), and ionic liquids (ILs). In addition, different types of microneedles, including 3D-printed microneedles, have been focused on in this review.
IFN-α/β Signaling Is Required for CDG-Mediated CTL Generation and B Lymphocyte Activation
Authors: Hamouda Ahmed E. I. , Schulze Kai , Ebensen Thomas , Guzmán Carlos Alberto , Lirussi Darío
Published: December 2022

Among cyclic di-nucleotides (CDN), both cyclic di-AMP (CDA) and di-GMP (CDG) are promising adjuvants and immune modulators. These molecules are not only able to induce profuse antibody production but also predominant T helper 1 and cytotoxic CD8 T lymphocytes (CTL) responses, which enable their use for vaccination against intracellular pathogens as well as in cancer immunotherapy. However, for their successful translation into the clinic, a comprehensive understanding of CDN mode of action is still essential. Consistent with evidence in the literature, we show here that IFN-α/β (Type I IFN) is crucial for CDG-mediated B cell activation. We recently determined the key role of type I IFN signaling for CDA-mediated enhancement of immunogenicity. Based on the biological activities of type I IFN, in this study, we hypothesized that it might also be required for CTL induction by CDG. We disclose here the mode of action of type I IFN signaling in CDG-mediated cross-presentation and subsequent CTL generation.
Extracellular Vesicles as Drug Targets and Delivery Vehicles for Cancer Therapy
Authors: Chitti Sai V. , Nedeva Christina , Manickam Raja , Fonseka Pamali , Mathivanan Suresh
Published: December 2022

Extracellular vesicles (EVs) are particles that are released from cells into the extracellular space both under pathological and normal conditions. It is now well established that cancer cells secrete more EVs compared to non-cancerous cells and that, captivatingly, several proteins that are involved in EV biogenesis and secretion are upregulated in various tumours. Recent studies have revealed that EVs facilitate the interaction between cancer cells and their microenvironment and play a substantial role in the growth of tumours. As EVs are involved in several aspects of cancer progression including angiogenesis, organotropism, pre-metastatic niche formation, fostering of metastasis, and chemoresistance, inhibiting the release of EVs from cancer and the surrounding tumour microenvironment cells has been proposed as an ideal strategy to treat cancer and associated paraneoplastic syndromes. Lately, EVs have shown immense benefits in preclinical settings as a novel drug delivery vehicle. This review provides a brief overview of the role of EVs in various hallmarks of cancer, focusing on (i) strategies to treat cancer by therapeutically targeting the release of tumour-derived EVs and (ii) EVs as valuable drug delivery vehicles. Furthermore, we also outline the drawbacks of the existing anti-cancer treatments and the future prospective of EV-based therapeutics.
Protein Modification Employing Non-Canonical Amino Acids to Prepare SUMOylation Detecting Bioconjugates
Authors: Williard Alexander C. , Switzer Hannah J. , Howard Christina A. , Yin Rui , Russell Brent L. , Sanyal Ritwik , Yu Shaun , Myers Trinity M. , Flood Brian M. , Kerscher Oliver , Young Douglas D.
Published: December 2022

Protein modification with non-canonical amino acids (ncAAs) represents a useful technology to afford homogenous samples of bioconjugates with site-specific modification. This technique can be directly applied to the detection of aberrant SUMOylation patterns, which are often indicative of disease states. Modified SUMO-trapping proteins, consisting of a catalytically inactive ULP1 fragment (UTAG) fused to the maltose-binding protein MBP, are useful reagents for the binding and labeling of SUMOylated proteins. Mutation of this UTAG fusion protein to facilitate amber suppression technologies for the genetic incorporation of ncAAs was assessed to provide a functional handle for modification. Ultimately, two sites in the maltose-binding protein (MBP) fusion were identified as ideal for incorporation and bioconjugation without perturbation to the SUMO-trapping ability of the UTAG protein. This functionality was then employed to label SUMOylated proteins in HeLa cells and demonstrate their enrichment in the nucleus. This modified UTAG-MBP-ncAA protein has far-reaching applications for both diagnostics and therapeutics.
A Cross-Sectional Survey Study Examining the Provision of Continuous Glucose Monitoring Education in U.S. Doctor of Pharmacy Programs
Authors: Knezevich Emily , Fuji Kevin T. , Larson Krysta , Muniz Gabrielle
Published: December 2022

Continuous glucose monitoring (CGM) is used to help patients with diabetes and their healthcare providers more effectively manage care. CGM use is expanding to all healthcare settings where pharmacists practice and new pharmacy graduates may increasingly be asked to assist patients utilizing CGM devices and assess diabetes management through the interpretation of CGM data. The purpose of this study was to describe CGM education across Doctor of Pharmacy (Pharm.D.) programs in the United States. An online survey was administered to 139 accredited Pharm.D. programs. Information was solicited about CGM education, including curricular placement, course type, hands-on experience, and credential(s) of faculty providing the education. Fifty-seven programs responded with 51 (89.5%) providing CGM education for a median of 1.0 h. Of programs providing detailed responses, content was delivered in required (60.4%) or elective (45.8%) lectures as well as experiential settings (41.7%). Education occurred most frequently in the third year (58.3%), followed by the second (43.8%) and fourth (37.5%) years. Thirty-one (66.0%) programs were taught by a faculty member with an advanced diabetes credential. The results from this study confirm that there is an ongoing need to examine optimal amount, timing, and methods for providing CGM education.
Non-Mechanical Multiplexed Beam-Steering Elements Based on Double-Sided Liquid Crystal Metasurfaces
Authors: Gorkunov Maxim V. , Geivandov Artur R. , Mamonova Alena V. , Simdyankin Ivan V. , Kasyanova Irina V. , Ezhov Alexander A. , Artemov Vladimir V.
Published: December 2022

We propose, optimize, fabricate and test beam-steering elements based on double-sided liquid-crystal (LC) metasurfaces allowing for diffractive and spectral multiplexing, and thus covering three different beam deflection directions each. While straightforward parallel design requires one diffractive beam-steering element per a direction determined by Bragg’s law, double-sided LC-metasurfaces are remarkably flexible and allow optimization for three operation modes at different applied voltages: zero-voltage mode with dominant +1 order red light and +2 order blue light diffraction; intermediate mode at 1.4–1.6 V voltage with dominant +1 order blue light diffraction; and transparent mode at 5 V voltage. We comprehensively study three such elements with 6, 8 and 10 micrometer periods and verify their capability of deflecting blue and red light beams with 40–70% efficiencies in nine target directions with 10 ms characteristic switching times.
Effect of Water-Induced and Physical Aging on Mechanical Properties of 3D Printed Elastomeric Polyurethane
Authors: Schwarz David , Pagáč Marek , Petruš Josef , Polzer Stanislav
Published: December 2022

In this study, the effect of moisture on the elastic and failure properties of elastomeric polyurethane (EPU 40) 3D printed via Vat Photopolymerization was investigated. EPU 40 samples were printed, and uniaxial tensile tests were performed on Dry-fresh, Dry-aged (eight months aged), and after various times of being immersed in water (0–8 months). Elastic response, initial stiffness, failure strength, and failure elongation were analyzed. Besides, gravimetric analysis was performed to determine the increase in weight and thickness after water immersion. The elastic response was fitted by the Arruda-Boyce constitutive model. Results show that initial stiffness decreased after immersion (mean 6.8 MPa dry vs. 6.3 MPa immersed p-value 0.002). Contrary, the initial stiffness increased due to physical aging under a dry state from a mean 6.3 MPa to 6.9 MPa (p = 0.006). The same effect was observed for stiffness parameter G of the constitutive model, while the limit stretch parameter λL was not affected by either aging. The 95% confidence intervals for strength and failure stretch were 5.27–9.48 MPa and 2.18–2.86, respectively, and were not affected either by immersion time or by physical aging. The median diffusion coefficient was 3.8·10−12 m^2/s. The immersion time has a significant effect only on stiffness, while oxidative aging has an inverse effect on the mechanical properties compared to water immersion. The transition process is completed within 24 h after immersion.