bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Novel LC-MS/MS Multi-Method for the Determination of Regulated and Emerging Food Contaminants Including Tenuazonic Acid, a Chromatographically Challenging Alternaria Toxin
Authors: Tölgyesi Ádám , Cseh Attila , Simon Andrea , Sharma Virender K.
Published: February 2023

The regulation of food contaminants in the European Union (EU) is comprehensive, and there are several compounds in the register or being added to the recommendation list. Recently, European standard methods for analysis have also been issued. The quick analysis of different groups of analytes in one sample requires a number of methods and the simultaneous use of various instruments. The aim of the present study was to develop a method that could analyze several groups of food contaminants: in this case, 266 pesticides, 12 mycotoxins, 14 alkaloid toxins, and 3 Alternaria toxins. The main advantage of the herein described approach over other methods is the simultaneous analysis of tenuazonic acid (TEA) and other relevant food contaminants. The developed method unites the newly published standard methods such as EN 15662:2018, EN 17194:2019, EN 17256:2019, EN 17425:2021, EN 17521:2021, which describes the analysis of both regulated and emerging contaminants. The developed method is based on a QuEChERS sample preparation, followed by LC-MS/MS analysis under alkaline mobile phase conditions. The pH of the aqueous eluent was set to 8.3, which resulted in baseline separation among ergot alkaloids and their corresponding epimers, a symmetric chromatographic peak shape for analyzing TEA and fit-for-purpose sensitivity for MS/MS detection in both positive and negative ionization modes. Those compounds, which possess the corresponding isotopically labeled internal standards (ISTD), allowed for direct quantification by the developed method and no further confirmation was necessary. This was proven by satisfactory analyses of a number of quality control (QC), proficiency test (PT), and validation samples.
Thermal Annealing Effect on Surface-Enhanced Raman Scattering of Gold Films Deposited on Liquid Substrates
Authors: Ye Ziran , Huang Haixia , Xu Fengyun , Lu Ping , Chen Yiben , Shen Jiawei , Ye Gaoxiang , Gao Fan , Yan Bo
Published: February 2023

We prepare metal films with various thicknesses on liquid substrates by thermal evaporation and investigate the annealing effect on these films. Gold films deposited on a silicone oil surface consist of a large number of branched aggregates, which contains plenty of gold nanoparticles. This characteristic morphology is mainly attributed to the isotropic and free-sustained liquid substrate. Thermal annealing results in the reintegration of nanoparticles; thus, the surface morphology and microstructure of gold films change significantly. The dependence of annealing conditions on the surface-enhanced Raman scattering performance of gold films is studied, in which gold films show favorable Raman activity when annealed at certain annealing temperature and the experimental results are verified by simulation analysis. The study on the optimal annealing temperature of surface-enhanced Raman scattering substrate will pave the way for the potential application of films deposited on liquid surfaces in microfluidics and enhanced Raman detection.
Biotechnology Advances in Bioremediation of Arsenic: A Review
Authors: Preetha Jaganathan Sakthi Yazhini , Arun Muthukrishnan , Vidya Nandakumar , Kowsalya Kumaresan , Halka Jayachandran , Ondrasek Gabrijel
Published: February 2023

Arsenic is a highly toxic metalloid widespread in the Earth's crust, and its contamination due to different anthropogenic activities (application of agrochemicals, mining, waste management) represents an emerging environmental issue. Therefore, different sustainable and effective remediation methods and approaches are needed to prevent and protect humans and other organisms from detrimental arsenic exposure. Among numerous arsenic remediation methods, those supported by using microbes as sorbents (microbial remediation), and/or plants as green factories (phytoremediation) are considered as cost-effective and environmentally-friendly bioremediation. In addition, recent advances in genetic modifications and biotechnology have been used to develop (i) more efficient transgenic microbes and plants that can (hyper)accumulate or detoxify arsenic, and (ii) novel organo-mineral materials for more efficient arsenic remediation. In this review, the most recent insights from arsenic bio-/phytoremediation are presented, and the most relevant physiological and molecular mechanisms involved in arsenic biological routes, which can be useful starting points in the creation of more arsenic-tolerant microbes and plants, as well as their symbiotic associations are discussed.
Methyl Jasmonate and Nanoparticles Doped with Methyl Jasmonate affect the Cell Wall Composition of Monastrell Grape Skins
Authors: Giménez-Bañón María José , Paladines-Quezada Diego Fernando , Moreno-Olivares Juan Daniel , Bleda-Sánchez Juan Antonio , Fernández-Fernández José Ignacio , Parra-Torrejón Belén , Ramírez-Rodríguez Gloria Belén , Delgado-López José Manuel , Gil-Muñoz Rocío
Published: February 2023

The structural composition of the cell wall of grape skins is related to the cell wall integrity and subsequent extraction of the different compounds that are contained inside vacuoles and also the cell wall breakdown products. Different reports have established that methyl jasmonate (MeJ) produces changes in the composition of the grape skin cell wall. The use of elicitors to promote the production of secondary metabolites in grapes has been studied in several reports; however, its study linked to nanotechnology is less developed. These facts led us to study the effect of methyl jasmonate (MeJ) and nanoparticles doped with MeJ (nano-MeJ) on the cell walls of Monastrell grapes during three seasons. Both treatments tended to increase cell wall material (CWM) and caused changes in different components of the skin cell walls. In 2019 and 2021, proteins were enlarged in both MeJ and nano-MeJ-treated grapes. A general decrease in total phenolic compounds was detected with both treatments, in addition to an increment in uronic acids when the grapes were well ripened. MeJ and nano-MeJ produced a diminution in the amount of cellulose in contrast to an increase in hemicellulose. It should be noted that the effects with nano-MeJ treatment occurred at a dose 10 times lower than with MeJ treatment.
Amyloid-like RIP1/RIP3 RHIM Fragments’ Characterization and Application as a Drug Depot
Authors: Ismail Maytham , Kanapathipillai Mathumai
Published: February 2023

Amyloid aggregates play a major role in diseases as well as in normal physiological function. Receptor-interacting protein kinases 1 and 3 (RIP1/RIP3) aggregates complexes in cellular necroptosis is one example of protein aggregation in normal cellular function. Although recently there have been several studies on full kinase proteins aggregation, the aggregation potential of small peptide sequences of RIP1/RIP3, the physicochemical properties, and the potential in biomedical applications have not been explored. Hence, in this paper, we study the aggregation propensity of peptides consisting of four and twelve amino acid sequences in the RHIM region of RIP1/RIP3 proteins that are known to drive the beta-sheet formation and the subsequent aggregation. The aggregation kinetics, physicochemical characterization, mechanosensitive properties, cellular effects, and potential as a cancer drug depot have been investigated. The results show that the number and concentration of amino acids play a role in amyloid-like aggregates’ properties. Further, the aggregates when formulated with cisplatin-induced significant lung cancer cell toxicity compared to an equal amount of cisplatin with and without ultrasound. The study would serve as a platform for further investigation on RIP1/RIP3 peptide and protein aggregates, their role in multiple cellular functions and diseases, and their potential as drug depots.
Novel Indole-Containing Hybrids Derived from Millepachine: Synthesis, Biological Evaluation and Antitumor Mechanism Study
Authors: Liang Baoxia , Zou Qing , Yu Lintao , Wang Yali , Yan Jun , Huang Baiqi
Published: February 2023

Millepachine, a bioactive natural product isolated from the seeds of Millettia pachycarpa, is reported to display potential antitumor activity. In this study, novel indole-containing hybrids derived from millepachine were designed, synthesized and evaluated for their antitumor activities. Among all the compounds, compound 14b exhibited the most potent cytotoxic activity against five kinds of human cancer cell lines, with IC50 values ranging from 0.022 to 0.074 μM, making it almost 100 times more active than millepachine. Valuable structure–activity relationships (SARs) were obtained. Furthermore, the mechanism studies showed that compound 14b induced cell-cycle arrest at the G2/M phase by inhibiting tubulin polymerization and further induced cell apoptosis through reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) collapse. In addition, the low cytotoxicity toward normal human cells and equivalent sensitivity towards drug-resistant cells of compound 14b highlighted its potential for the development of antitumor drugs.
Characterization and Comparison of Extra Virgin Olive Oils of Turkish Olive Cultivars
Authors: Korkmaz Aziz
Published: February 2023

Extra virgin olive oils (EVOOs) obtained from five Turkish olive cultivars widely produced in the Aegean and Marmara regions were investigated based on their total antioxidant capacity (TAC), total phenolic content (TPC), pigment contents, fatty acid (FA) profiles, phenolic compounds (PC), volatile compounds (VC), and sensory properties. The results showed that all properties of EVOO samples were significantly affected by the olive cultivar used. The pigment contents in Ayvalık (9.90 mg·kg−1) and Uslu (9.00 mg·kg−1) oils were higher than the others (p < 0.05). The greatest values for oleic acid (74.13%) and TPC (350.6 mg·kg−1) were observed in Gemlik and Domat oils, respectively (p < 0.05). Edincik oil showed the maximum hydroxytyrosol content (48.022 mg·kg−1) and TAC value (515.36 mg TE·kg−1) (p < 0.05). The Edincik, Domat, and Uslu oils were significantly not different for the total content of C6 compounds derived by lipoxygenase, which are the main volatiles responsible for the typical aroma of EVOOs (p > 0.05). Domat oil also exhibited the highest scores for bitterness and pungency perceptions (p < 0.05). The fruitiness scores of the oil samples (except for Ayvalık oil) were close to each other, even if they were statistically different (p < 0.05). Principal component analysis (PCA) indicated that the Ayvalık oil was separated from the others due to its poor-quality characteristics. As a result, it can be stated that Domat olive oil has better quality than the others.
The Quest for Green Solvents for the Sustainable Production of Nanosheets of Two-Dimensional (2D) Materials, a Key Issue in the Roadmap for the Ecology Transition in the Flatland
Authors: Occhiuzzi Jessica , Politano Grazia Giuseppina , D’Olimpio Gianluca , Politano Antonio
Published: February 2023

The recent advent of two-dimensional (2D) materials has had a ground-breaking impact on science and technology. To exploit in technology their unique thickness-dependent physicochemical properties, the large-scale production of 2D materials is mandatory, but it represents an open challenge still due to various pitfalls and severe limitations including the toxicity of state-of-the-art solvents. Thus, liquid-phase exfoliation based on green and bioderived solvents represents an ideal methodology for massive production. This is particularly crucial for introducing 2D materials in technological applications such as the production of drinking water and agri-food industrial processes. Here, we assessed the production of 2D nanosheets (specifically, graphene, WS2, MoS2) with liquid-phase exfoliation assisted by eco-friendly solvents, with a comparative evaluation of green solvents in terms of the yield and, moreover, the aspect ratio, defectivity, and crystalline quality of the produced nanosheets. In particular, we focus on the most promising green solvents in terms of the yield and the crystalline quality of the produced nanosheets: Polarclean, Iris, and Cyrene, which were compared with acetone/water mixtures, isopropyl alcohol (IPA), triethanolamine (TEA), aqueous solutions of urea, and an ethanol/water mixture as well as two toxic solvents largely used for the production of 2D nanosheets: N-methyl-2-pyrrolidone (NMP) and N, N-dimethylformamide (DMF). Remarkably, the density of defects was particularly low in the liquid-phase exfoliation with Polarclean, as indicated by the Raman spectrum of graphene, with the I(D)/I(G) ratio below 0.1. Furthermore, Polarclean and Iris also enable ink-jet printing with functional inks of 2D materials based on green solvents due to their low dynamic viscosity at room temperature.
Anti-Neuroinflammatory Potential of Natural Products in the Treatment of Alzheimer’s Disease
Authors: Deng Mingzhenlong , Yan Wanli , Gu Zhicheng , Li Yan , Chen Lei , He Bin
Published: February 2023

Alzheimer’s disease (AD) is an age-related chronic progressive neurodegenerative disease, which is the main cause of dementia in the elderly. Much evidence shows that the onset and late symptoms of AD are caused by multiple factors. Among them, aging is the main factor in the pathogenesis of AD, and the most important risk factor for AD is neuroinflammation. So far, there is no cure for AD, but the relationship between neuroinflammation and AD may provide a new strategy for the treatment of AD. We herein discussed the main etiology hypothesis of AD and the role of neuroinflammation in AD, as well as anti-inflammatory natural products with the potential to prevent and alleviate AD symptoms, including alkaloids, steroids, terpenoids, flavonoids and polyphenols, which are available with great potential for the development of anti-AD drugs.
A Knowledge-Graph-Based Multimodal Deep Learning Framework for Identifying Drug–Drug Interactions
Authors: Zhang Jing , Chen Meng , Liu Jie , Peng Dongdong , Dai Zong , Zou Xiaoyong , Li Zhanchao
Published: February 2023

The identification of drug–drug interactions (DDIs) plays a crucial role in various areas of drug development. In this study, a deep learning framework (KGCN_NFM) is presented to recognize DDIs using coupling knowledge graph convolutional networks (KGCNs) with neural factorization machines (NFMs). A KGCN is used to learn the embedding representation containing high-order structural information and semantic information in the knowledge graph (KG). The embedding and the Morgan molecular fingerprint of drugs are then used as input of NFMs to predict DDIs. The performance and effectiveness of the current method have been evaluated and confirmed based on the two real-world datasets with different sizes, and the results demonstrate that KGCN_NFM outperforms the state-of-the-art algorithms. Moreover, the identified interactions between topotecan and dantron by KGCN_NFM were validated through MTT assays, apoptosis experiments, cell cycle analysis, and molecular docking. Our study shows that the combination therapy of the two drugs exerts a synergistic anticancer effect, which provides an effective treatment strategy against lung carcinoma. These results reveal that KGCN_NFM is a valuable tool for integrating heterogeneous information to identify potential DDIs.
Microbial Production of Human Milk Oligosaccharides
Authors: Palur Dileep Sai Kumar , Pressley Shannon R. , Atsumi Shota
Published: February 2023

Human milk oligosaccharides (HMOs) are complex nonnutritive sugars present in human milk. These sugars possess prebiotic, immunomodulatory, and antagonistic properties towards pathogens and therefore are important for the health and well-being of newborn babies. Lower prevalence of breastfeeding around the globe, rising popularity of nutraceuticals, and low availability of HMOs have inspired efforts to develop economically feasible and efficient industrial-scale production platforms for HMOs. Recent progress in synthetic biology and metabolic engineering tools has enabled microbial systems to be a production system of HMOs. In this regard, the model organism Escherichia coli has emerged as the preferred production platform. Herein, we summarize the remarkable progress in the microbial production of HMOs and discuss the challenges and future opportunities in unraveling the scope of production of complex HMOs. We focus on the microbial production of five HMOs that have been approved for their commercialization.
Facile Preparation of Cellulose Aerogels with Controllable Pore Structure
Authors: Qiu Jiahao , Guo Xingzhong , Lei Wei , Ding Ronghua , Zhang Yun , Yang Hui
Published: February 2023

Cellulose aerogels are the latest generation of aerogels and have also received extensive attention due to their renewable and biocompatible properties. Herein, cellulose aerogel was facilely prepared by using NaOH/urea solution as solvent, raising the temperature to control gelation and drying wet gel sequentially. With NaOH/urea solution as solvent, the cellulose concentration has an important impact on the micromorphology of cellulose aerogels, while the aging time rarely affects the micromorphology. The appropriate solvent and drying method allow the formation of different cellulose crystalline structures. Different from the Cellulose Ⅰ crystalline structure of raw cellulose powder, the cellulose phase of as-prepared cellulose aerogels belongs to the Cellulose Ⅱ crystalline structure, and to some extent the pyrolysis temperature is also lower than that of raw cellulose powder. The resultant cellulose aerogel prepared by using NaOH/urea solution as solvent and freeze-drying has a uniform macroporous structure with a macropore size of 1~3 µm.
Overview of Systematic Reviews of Health Interventions for the Prevention and Treatment of Overweight and Obesity in Children
Authors: Denova-Gutiérrez Edgar , González-Rocha Alejandra , Méndez-Sánchez Lucía , Araiza-Nava Berenice , Balderas Nydia , López Giovanna , Tolentino-Mayo Lizbeth , Jauregui Alejandra , Hernández Lucia , Unikel Claudia , Bonvecchio Anabelle , Shamah Teresa , Barquera Simón , Rivera Juan A.
Published: February 2023

(1) Background: The importance of studying the health interventions used to prevent and treat overweight and obesity in school-aged children is imperative. This overview aimed to summarize systematic reviews that assess the effects of school-based, family, and mixed health interventions for preventing and treating overweight and obesity in school-aged children. (2) Methods: The Cochrane Collaboration methodology and PRISMA statement were followed. A search was conducted using terms adapted to 12 databases. Systematic reviews reporting interventions in children from six to 12 years old with an outcome related to preventing or treating obesity and overweight were included. Studies with pharmacological or surgical interventions and adolescents were excluded. (3) Results: A total of 15,226 registers were identified from databases and citation searching. Of those, ten systematic reviews published between 2013 and 2022 were included. After the overlap, 331 interventions for children between 6 and 12 years old were identified, and 61.6% involved physical activity and nutrition/diet intervention. Multicomponent intervention, combining physical activity with nutrition and behavioral change, school-based plus community-based interventions may be more effective in reducing overweight and obesity in children. (4) Conclusions: Plenty of interventions for childhood overweight and obesity aimed at prevention and treatment were identified, but there is a gap in the methodological quality preventing the establishment of a certain recommendation.
The Association of Serum and Dietary Magnesium with Depressive Symptoms
Authors: Chou Ming-Hui , Yang Yen Kuang , Wang Jung-Der , Lin Chung-Ying , Lin Sheng-Hsiang
Published: February 2023

Depression is a leading cause of the global burden of disease and has a multifactorial etiology that includes nutrients. Magnesium status has been associated with depression with inconclusive results. The impact of chronic latent magnesium deficiency (CLMD, 0.75 ≤ serum magnesium < 0.85 mmol/L) on depression has not yet been investigated. We assessed the association between serum magnesium levels/dietary magnesium intake and depressive symptoms by analyzing nationally representative data from Taiwan (Nutrition and Health Survey in Taiwan, NAHSIT). We used the 5-item Brief Symptom Rating Scale to measure depressive symptoms. Subgroup analysis by sex was also performed. Serum magnesium levels had a low correlation with dietary magnesium intake. Higher serum magnesium levels were associated with lower depressive scores and a lower risk of depressive symptoms, but dietary magnesium intake showed no association. Sex differences were found. Compared with subjects with serum magnesium <0.75 mmol/L, those with ≥0.85 mmol/L had lower depressive scores. In conclusion, serum magnesium was inversely associated with depressive symptoms, but dietary magnesium intake was not. Subjects with CLMD showed similar depressive scores and were at a similar risk of depressive symptoms to those with serum magnesium < 0.75 mmol/L. CLMD should be considered while assessing the association between magnesium status and depressive symptoms.
Acute Dose–Response Effectiveness of Combined Catechins and Chlorogenic Acids on Postprandial Glycemic Responses in Healthy Men: Results from Two Randomized Studies
Authors: Yanagimoto Aya , Matsui Yuji , Yamaguchi Tohru , Saito Shinichiro , Hanada Ryuzo , Hibi Masanobu
Published: February 2023

Epidemiologic studies show that the risk of diabetes can be reduced by ingesting green tea or coffee. Previous studies have shown that simultaneously taking green tea catechins (GTC) and coffee chlorogenic acid (CCA) alters postprandial gastrointestinal hormones secretion and improves insulin sensitivity. However, there is no evidence on the acute effects of GTC and CCA on incretin and blood glucose, and on the respective dose of polyphenols. In this randomized, double-blind, placebo-controlled crossover study, we examined the effective dose of GTC and CCA on postprandial glucose, insulin, and incretin responses to a high-fat and high-carbohydrate cookie meal containing 75 g of glucose in healthy men. Study 1 (n = 18) evaluated two doses of GTC (270 or 540 mg) containing a fixed dose of CCA (270 mg) with 113 mg of caffeine and a placebo (0 mg GTC and 0 mg CCA) with 112 mg of caffeine. Study 2 (n = 18) evaluated two doses of CCA (150 or 300 mg) containing a fixed dose of GTC (540 mg) and a placebo with 99 mg of caffeine. The single combined ingestion of GTC and CCA significantly altered the incretin response and suppressed glucose and insulin levels. These findings suggest that the effective minimum dose is 540 mg of GTC and 150 mg of CCA.
Emotional Eating and Changes in High-Sugar Food and Drink Consumption Linked to Psychological Distress and Worries: A Cohort Study from Norway
Authors: Javadi Arjmand Elaheh , Bemanian Mitra , Vold Jørn Henrik , Skogen Jens Christoffer , Sandal Gro Mjeldheim , Arnesen Erik K. , Mæland Silje , Fadnes Lars Thore
Published: February 2023

Psychological distress is linked to unhealthy eating behaviors such as emotional eating and consumption of high-sugar food and drinks. Cross-sectional studies from early in the COVID-19 pandemic showed a high occurrence of worries and psychological distress, and this was associated with emotional eating. Few larger studies have examined how this coping pattern develops over time. This cohort study with 24,968 participants assessed changes over time in emotional eating, consumption of sugary foods as an example of unhealthy food choices, and consumption of fruits and vegetables as an example of healthy food choices. Further, associations between these and psychological distress, worries, and socio-demographic factors were assessed. Data were collected at three time points (April 2020, initially in the COVID-19 pandemic, then one and two years later). Emotional eating and intake of sugary foods and drinks were high at the start of the pandemic, followed by a reduction over time. High psychological distress was strongly associated with higher levels of emotional eating and high-sugar food intake, and lower levels of healthy eating habits. The strength of this association reduced over time. Our findings indicate the high frequency in unhealthy food choices seen early in the COVID-19 pandemic improved over time.
Chloride, Sodium and Calcium Intake Are Associated with Mortality and Follow-Up Kidney Function in Critically Ill Patients Receiving Continuous Veno-Venous Hemodialysis—A Retrospective Study
Authors: Hellman Tapio , Uusalo Panu , Järvisalo Mikko J.
Published: February 2023

Background: Studies on the association between solute, nutrition and fluid intakes and mortality and later kidney function in critically ill acute kidney injury (AKI) patients receiving continuous veno-venous hemodialysis (CVVHD) are scarce. Methods: Altogether, 471 consecutive critically ill AKI patients receiving CVVHD in the research intensive care unit (ICU) were recruited in this single-center, retrospective study. Results: The median age was 66 (58–74) years, and 138 (29.3%) were female. The 90-day and one-year mortalities were 221 (46.9%) and 251 (53.3%), respectively. After adjusting for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE) score, coronary artery disease, immunosuppression, ICU care duration, mechanical ventilation requirement, vasopressor requirement and study time period, the cumulative daily intake of potassium, chloride, sodium, phosphate, calcium, glucose, lipids and water was associated with one-year mortality in separate multivariable cox proportional hazards models. In a sensitivity analysis excluding patients who died within the first three days of ICU care, the daily intake of chloride (hazard ratio (HR) 1.001, confidence interval (CI) 95% 1.000–1.003, p = 0.032), sodium (HR 1.001, CI 95% 1.000–1.002, p = 0.031) and calcium (HR 1.129, CI 95% 1.025–1.243, p = 0.014) remained independently associated with mortality within one-year in the respective, similarly adjusted multivariable cox analyses. The cumulative daily intake of chloride, sodium, calcium and water was independently associated with the estimated glomerular filtration rate (eGFR) at 90 days follow-up in separate substantially adjusted multivariable cox proportional hazards models. Conclusion: The cumulative daily intake of chloride, sodium and calcium is associated with mortality and daily chloride, sodium, calcium and water intake is associated with follow-up eGFR in critically ill patients with CVVHD-treated AKI.
Yarning about Diet: The Applicability of Dietary Assessment Methods in Aboriginal and Torres Strait Islander Australians—A Scoping Review
Authors: Davies Alyse , Coombes Julieann , Wallace Jessica , Glover Kimberly , Porykali Bobby , Allman-Farinelli Margaret , Kunzli-Rix Trinda , Rangan Anna
Published: February 2023

Conventional dietary assessment methods are based predominately on Western models which lack Aboriginal and Torres Strait Islander knowledges, methodologies, and social and cultural contextualisation. This review considered dietary assessment methods used with Aboriginal and Torres Strait Islander populations and assessed their applicability. Four electronic databases and grey literature were searched with no time limit applied to the results. Screening, data extraction and quality appraisal were undertaken independently by two reviewers. Out of 22 studies, 20 were conducted in rural/remote settings, one in an urban setting, and one at the national population level. The most frequently used and applicable dietary assessment method involved store data. Weighed food records and food frequency questionnaires had low applicability. Modifications of conventional methods were commonly used to adapt to Indigenous practices, but few studies incorporated Indigenous research methodologies such as yarning. This highlights an opportunity for further investigation to validate the accuracy of methods that incorporate qualitative yarning-based approaches, or other Indigenous research methodologies, into quantitative data collection. The importance of developing validated dietary assessment methods that are appropriate for this population cannot be understated considering the high susceptibility to nutrition-related health conditions such as malnutrition, overweight or obesity, diabetes, and cardiovascular disease.
Comparison of Oxygen Electrode Chronoamperometry and Spectrophotometry for Determination of Catalase Activity
Authors: Szczepanczyk Michal , Paul Lea , Ruzgas Tautgirdas , Björklund Sebastian
Published: February 2023

Catalase is a key antioxidative enzyme, and a deficiency or malfunction of catalase is hypothesized to be related to various diseases. To investigate catalase activity, it is important to use reliable methods and experimental protocols enabling consistent fallouts. One major problem, however, is that the activity values obtained with different techniques and procedures can vary to a large extent. The aim of this work was to identify experimental conditions that provide similar catalase activity values with two different methods based on either spectrophotometry or chronoamperometry. The investigated parameters include the concentration of catalase and its substrate (H2O2), as well as the effect of deoxygenation of the catalase medium by nitrogen (N2). Within the frame of investigated conditions, we show that spectrophotometry is strongly affected by the catalase concentration, whereas chronoamperometry is shown to be more dependent on the substrate concentration. Deoxygenation leads to elevated catalase activity values in the case of chronoamperometry, whereas it shows no influence on the results obtained with spectrophotometry. In particular, in the case of low substrate concentrations (i.e., low catalase reaction rates), higher and more accurate results are obtained with deoxygenation in the case of chronoamperometry measurements due to minimized oxygen escape. The effect of deoxygenation, giving rise to elevated catalase activity values, however, is not statistically significant at high substrate concentrations, implying that the protocol can be simplified by excluding this step as long as the other parameters are optimized. Finally, by comparing the two methods at different experimental conditions, we identified protocols resulting in similar results, i.e., 10 mM H2O2 and catalase activity of 4–5 U/mL. Based on this work, improved consistency of catalase activity data obtained with different methodologies and in different labs is expected.
Haplotype Analysis Sheds Light on the Genetic Evolution of the Powdery Mildew Resistance Locus Pm60 in Triticum Species
Authors: Huang Xuhui , Jin Xueli , Ren Xiaojie , Wu Wenxuan , Ji Wenjun , Feng Lihua , Jiang Bo , Hao Ming , Ning Shunzong , Yuan Zhongwei , Zhang Lianquan , Wu Bihua , Liu Dengcai , Wei Zhen-Zhen , Huang Lin
Published: February 2023

Wheat powdery mildew (Blumeria graminis f. sp. tritici, Bgt, recently clarified as B. graminis s. str.), is one of the most destructive diseases of wheat. Pm60 is a nucleotide-binding leucine-rich repeat (NLR) gene that confers race-specific resistance to Bgt. Allelic variants (Pm60, Pm60a, and Pm60b) were found in Triticum urartu and T. dicoccoides, the wild progenitors of wheat. In the present study, we studied the diversity of the Pm60 locus in a large set of wheat germplasm and found 20 tetraploid wheats harboring the Pm60 alleles, which correspond to three novel haplotypes (HapI–HapIII). HapI (Pm60 allele) and HapII (Pm60a allele) were present in domesticated tetraploid wheats, whereas HapIII (Pm60a allele) was identified in wild tetraploid T. araraticum. A sequence comparison of HapII and HapIII revealed that they differed by three SNPs and a GCC deletion. Results of the phylogenetic analysis revealed that HapII was more closely related to the functional haplotype MlIW172. Infection tests showed that HapII-carrying lines display a partial resistance response to Bgt#GH, while HapI was susceptible. Our results provide insights into the genetic evolution of the Pm60 locus and potential valuable alleles for powdery mildew resistance breeding.
SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants
Authors: Reeg David B. , Hofmann Maike , Neumann-Haefelin Christoph , Thimme Robert , Luxenburger Hendrik
Published: February 2023

Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T cells being linked to efficient viral clearance. Vaccination against SARS-CoV-2 induces both CD4+ and CD8+ T cell responses and permits protection from severe COVID-19, including infection with the currently circulating variants of concern. Nevertheless, in immunocompromised individuals, first data imply significantly impaired SARS-CoV-2-specific immune responses after both natural infection and vaccination. Hence, these high-risk groups require particular consideration, not only in routine clinical practice, but also in the development of future vaccination strategies. In order to assist physicians in the guidance of immunocompromised patients, concerning the management of infection or the benefit of (booster) vaccinations, this review aims to provide a concise overview of the current knowledge about SARS-CoV-2-specific cellular immune responses in the vulnerable cohorts of cancer patients, people living with HIV (PLWH), and solid organ transplant recipients (SOT). Recent findings regarding the virus-specific cellular immunity in these differently immunocompromised populations might influence clinical decision-making in the future.
Unrevealing the Mystery of Latent Leishmaniasis: What Cells Can Host Leishmania?
Authors: Valigurová Andrea , Kolářová Iva
Published: February 2023

Leishmania spp. (Kinetoplastida) are unicellular parasites causing leishmaniases, neglected tropical diseases of medical and veterinary importance. In the vertebrate host, Leishmania parasites multiply intracellularly in professional phagocytes, such as monocytes and macrophages. However, their close relative with intracellular development—Trypanosoma cruzi—can unlock even non-professional phagocytes. Since Leishmania and T. cruzi have similar organelle equipment, is it possible that Leishmania can invade and even proliferate in cells other than the professional phagocytes? Additionally, could these cells play a role in the long-term persistence of Leishmania in the host, even in cured individuals? In this review, we provide (i) an overview of non-canonical Leishmania host cells and (ii) an insight into the strategies that Leishmania may use to enter them. Many studies point to fibroblasts as already established host cells that are important in latent leishmaniasis and disease epidemiology, as they support Leishmania transformation into amastigotes and even their multiplication. To invade them, Leishmania causes damage to their plasma membrane and exploits the subsequent repair mechanism via lysosome-triggered endocytosis. Unrevealing the interactions between Leishmania and its non-canonical host cells may shed light on the persistence of these parasites in vertebrate hosts, a way to control latent leishmaniasis.
A Review of Major Patents on Potential Malaria Vaccine Targets
Authors: Mariano Reysla Maria da Silveira , Gonçalves Ana Alice Maia , Oliveira Diana Souza de , Ribeiro Helen Silva , Pereira Diogo Fonseca Soares , Santos Ingrid Soares , Lair Daniel Ferreira , Silva Augusto Ventura da , Galdino Alexsandro Sobreira , Chávez-Fumagalli Miguel Angel , Silveira-Lemos Denise da , Dutra Walderez Ornelas , Giunchetti Rodolfo Cordeiro
Published: February 2023

Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite’s complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite’s replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle.
Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies
Authors: Rehman Najeeb Ur , Ullah Saeed , Alam Tanveer , Halim Sobia Ahsan , Mohanta Tapan Kumar , Khan Ajmal , Anwar Muhammad U. , Csuk René , Avula Satya Kumar , Al-Harrasi Ahmed
Published: February 2023

A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA (1)) and 11-keto-β-boswellic acid (β-KBA (2)) was designed and synthesized by employing “click” chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate 3 or β-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a–5k in the presence of copper iodide (CuI) and Hünig’s base furnished the desired products—1H-1,2,3-triazole hybrids of β-AKBA (6a–6k) and β-KBA (7a–7k)—in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 µM. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.
Role of Neoadjuvant Immune Checkpoint Inhibitors in Resectable Non-Small Cell Lung Cancer
Authors: Riano Ivy , Abuali Inas , Sharma Aditya , Durant Jewelia , Dragnev Konstantin H.
Published: February 2023

The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/− radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and effective therapeutic strategy for the treatment of advanced NSCLC. Therefore, it is possible that ICIs for early-stage NSCLC may follow the pattern established in metastatic disease. Currently, there are several ongoing trials to determine the efficacy in the neoadjuvant setting for patients with local or regional disease. To date, only nivolumab in combination with chemotherapy has been approved by the U.S. FDA in the preoperative setting, but data continue to evolve rapidly, and treatment guidelines need to be determined. In this article, we review the current preclinical and clinical evidence on neoadjuvant ICIs alone and combination in the treatment of early-stage NSCLC.
Turning Microbial AhR Agonists into Therapeutic Agents via Drug Delivery Systems
Authors: Puccetti Matteo , Pariano Marilena , Wojtylo Paulina , Schoubben Aurélie , Giovagnoli Stefano , Ricci Maurizio
Published: February 2023

Developing therapeutics for inflammatory diseases is challenging due to physiological mucosal barriers, systemic side effects, and the local microbiota. In the search for novel methods to overcome some of these problems, drug delivery systems that improve tissue-targeted drug delivery and modulate the microbiota are highly desirable. Microbial metabolites are known to regulate immune responses, an observation that has resulted in important conceptual advances in areas such as metabolite pharmacology and metabolite therapeutics. Indeed, the doctrine of “one molecule, one target, one disease” that has dominated the pharmaceutical industry in the 20th century is being replaced by developing therapeutics which simultaneously manipulate multiple targets through novel formulation approaches, including the multitarget-directed ligands. Thus, metabolites may not only represent biomarkers for disease development, but also, being causally linked to human diseases, an unexploited source of therapeutics. We have shown the successful exploitation of this approach: by deciphering how signaling molecules, such as the microbial metabolite, indole-3-aldehyde, and the repurposed drug anakinra, interact with the aryl hydrocarbon receptor may pave the way for novel therapeutics in inflammatory human diseases, for the realization of which drug delivery platforms are instrumental.
Hybrid Manufacturing of Oral Solid Dosage Forms via Overprinting of Injection-Molded Tablet Substrates
Authors: Xu Han , Ebrahimi Farnoosh , Gong Ke , Cao Zhi , Fuenmayor Evert , Major Ian
Published: February 2023

Since 3D printing allows for patient-specific dosage forms, it has become a major focus in pharmaceutical research. However, it is difficult to scale up drug product manufacturing. Injection molding has been used in conjunction with hot-melt extrusion to mass produce drug products, but making tailored solid dosage forms with this technology is neither cost-effective nor simple. This study explored the use of a combination of fused filament fabrication and injection molding to create patient-specific solid dosage forms. A tablet fixation and location template was used to overprint directly on injection-molded tablet bases, and theophylline was combined with polycaprolactone and Kollidon® VA64 via hot-melt extrusion to produce the filament. Dynamic mechanical analysis was used to evaluate the brittleness of the filament, and differential scanning calorimetry was used to analyze the thermal results. The results showed that theophylline had a flow promoting effect on the polymer blend and that overprinted tablets were manufactured faster than 3D-printed tablets. Drug release studies also showed that overprinted tablets released faster than injection-molded tablets. This method demonstrates the potential of hybrid manufacturing for the pharmaceutical industry as a means of bridging the gap between personalized dosage forms and mass production.
Relationship between Body Composition and Serum Immunoglobulin Concentrations after Administration of Intravenous Immune Globulin–Preclinical and Clinical Evidence
Authors: Brunetti Luigi , Chapy Helene , Nahass Ronald G. , Moore Rebecca , Wassef Andrew , Adler Derek , Yurkow Edward , Kagan Leonid
Published: February 2023

The purpose of this study was to investigate the effect of obesity on immunoglobulin G (IgG) pharmacokinetics in a rat model of obesity, and to collect clinical evidence for an association between the body composition and intravenous immune globulin (IVIG) pharmacokinetic parameters in humans. In a preclinical study, pharmacokinetics of human IgG was evaluated after intravenous (IV) and subcutaneous (SC) delivery to obese and lean rats (n = 6 in each group). Serial serum samples were analyzed using an ELISA. The animal body composition was assessed using computer tomography. Patients with primary immunodeficiency currently managed with IVIG, and at a steady state, were enrolled in the clinical study (n = 8). Serum immune globulin (Ig) concentrations were measured at baseline and immediately after the administration of two consecutive treatments, with an additional measurement at two weeks after the first administration. In addition to the patient demographic and clinical characteristics, body composition was measured using bioelectrical impedance analysis. The pharmacokinetics of human IgG was significantly different between the obese and lean rats after both the IV and SC administration of 0.5 g/kg. Furthermore, a significant difference in endogenous rat IgG was observed between the two strains. In the human study, total serum IgG and subtype (IgG1, IgG2, IgG3, IgG4) half-life negatively correlated with the body mass index and fat mass. The mean change in the total serum IgG concentration was significantly correlated to body mass index and fat mass. The results of the studies corroborated one another. In the animal study, most pharmacokinetic parameters of human IgG following IV and SC administration were significantly affected by obesity and changes in the body composition. In the clinical study, the mean serum IgG change after the IVIG administration strongly correlated to the BMI and body fat mass. Future studies are needed to establish the outcomes achieved with more frequent dosing in obese individuals with primary immunodeficiency.