bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of the Impact Pathways of Biofortified Foods and Food Products
Authors: Huey Samantha L. , Krisher Jesse T. , Bhargava Arini , Friesen Valerie M. , Konieczynski Elsa M. , Mbuya Mduduzi N. N. , Mehta Neel H. , Monterrosa Eva , Nyangaresi Annette M. , Mehta Saurabh
Published: March 2022

Biofortification is the process of increasing the concentrations and/or bioavailability of micronutrients in staple crops and has the potential to mitigate micronutrient deficiencies globally. Efficacy trials have demonstrated benefits of consuming biofortified crops (BFCs); and in this paper, we report on the results of a systematic review of biofortified crops effectiveness in real-world settings. We synthesized the evidence on biofortified crops consumption through four Impact Pathways: (1) purchased directly; (2) in informal settings; (3) in formal settings; or (4) in farmer households, from their own production. Twenty-five studies, covering Impact Pathway 1 (five studies), Impact Pathway 2 (three), Impact Pathway 3 (three), Impact Pathway 4 (21) were included. The review found evidence of an improvement in micronutrient status via Impact Pathway 4 (mainly in terms of vitamin A from orange sweet potato) in controlled interventions that involved the creation of demand, the extension of agriculture and promotion of marketing. In summary, evidence supports that biofortified crops can be part of food systems interventions to reduce micronutrient deficiencies in farmer households; ongoing and future research will help fully inform their potential along the other three Impact Pathways for scaling up.
Distinct Effects of High-Fat and High-Phosphate Diet on Glucose Metabolism and the Response to Voluntary Exercise in Male Mice
Authors: Vidal Pablo , Baer Lisa A. , Félix-Soriano Elisa , Yang Felix T. , Branch Daniel A. , Baskin Kedryn K. , Stanford Kristin I.
Published: March 2022

The prevalence of metabolic diseases is rapidly increasing and a principal contributor to this is diet, including increased consumption of energy-rich foods and foods with added phosphates. Exercise is an effective therapeutic approach to combat metabolic disease. While exercise is effective to combat the detrimental effects of a high-fat diet on metabolic health, the effects of exercise on a high-phosphate diet have not been thoroughly investigated. Here, we investigated the effects of a high-fat or high-phosphate diet in the presence or absence of voluntary exercise on metabolic function in male mice. To do this, mice were fed a low-fat, normal-phosphate diet (LFPD), a high-phosphate diet (HPD) or a high-fat diet (HFD) for 6 weeks and then subdivided into either sedentary or exercised (housed with running wheels) for an additional 8 weeks. An HFD severely impaired metabolic function in mice, increasing total fat mass and worsening whole-body glucose tolerance, while HPD did not induce any notable effects on glucose metabolism. Exercise reverted most of the detrimental metabolic adaptations induced by HFD, decreasing total fat mass and restoring whole-body glucose tolerance and insulin sensitivity. Interestingly, voluntary exercise had a similar effect on LFPD and HPD mice. These data suggest that a high-phosphate diet does not significantly impair glucose metabolism in sedentary or voluntary exercised conditions.
Comparative Study on Nutrition and Lifestyle of Information Technology Workers from Romania before and during COVID-19 Pandemic
Authors: Nasui Bogdana Adriana , Toth Andreea , Popescu Codruta Alina , Penes Ovidiu Nicolae , Varlas Valentin Nicolae , Ungur Rodica Ana , Ciuciuc Nina , Silaghi Cristina Alina , Silaghi Horatiu , Pop Anca Lucia
Published: March 2022

The study aimed to evaluate lifestyle factors among Information Technology (IT) workers from Romania before and during the pandemic. We used an online applied questionnaire, filled in by 1638 respondents, that assessed nutrition status-Body Mass Index (BMI), weight and diet change, physical activity, alcohol consumption, number of hours working in front of the computer, stress, and sleep. Multivariate logistic regression was used to establish the lifestyle factors that lead to weight gain. Although the level of physical activity (PA) was low before the pandemic, the results of our study showed a further decrease in physical activity. In total, 61.1% of men and 71.1% of women performed PA for less than 30 min per day. Weight gain was reported in 50.5% of men and 45.3% of women (mean weight gain was 5.11 ± 3.52 kg) as a result of increased screen time (with a mean of 3.52 ± 4.29 for females and 3.05 ± 2.09 for males, p > 0.05 h per day) and the reported changes in diet. Despite the popularity of home-cooked foods, the intake of vegetables and fruit remained low. The quality of sleep was poor for 55.7% of the respondents. Public health and corporation policies are required to encourage a healthy lifestyle and avoid chronic diseases.
The Impact of the COVID-19 Pandemic on Food Consumption Behavior: Based on the Perspective of Accounting Data of Chinese Food Enterprises and Economic Theory
Authors: Yang Chung-Cheng , Chen Yahn-Shir , Chen Jianxiong
Published: March 2022

Since the outbreak of the COVID-19 pandemic, the rapid spread of COVID-19 around the world has become one of the main focuses of concern in almost every country, and governments have taken numerous measures to prevent/mitigate the spread of the disease. As an essential social determinant, COVID-19 has significantly impacted consumers’ food consumption behavior and healthy eating habits/behaviors. The purpose of this study is to analyze the impact of COVID-19 on food consumption behavior, and the main goal was to assess the possible problems (such as food waste and weight gain) caused by changes in food consumption behavior during the pandemic. Based on the accounting data of Chinese enterprises found in the China Stock Market and Accounting Research (CSMAR) database, this study uses economic theory and the translog function to conduct an average partial effect (APE) analysis of the pandemic, and finds that the COVID-19 pandemic has increased Chinese people’s overall food consumption, and the consumption of food from large food enterprises has increased even more (APE = 0.11 vs. APE = 0.31). This study suggests that food waste and weight gain in the Chinese population may be more severe during the pandemic, and it is necessary to enhance food management and weight management through multiple pathways.
Nutrition Interventions for Children with Cerebral Palsy in Low- and Middle-Income Countries: A Scoping Review
Authors: Jahan Israt , Sultana Risad , Muhit Mohammad , Akbar Delwar , Karim Tasneem , Al Imam Mahmudul Hassan , Das Manik Chandra , Smithers-Sheedy Hayley , McIntyre Sarah , Badawi Nadia , Khandaker Gulam
Published: March 2022

Background: Malnutrition is substantially higher among children with cerebral palsy (CP) in low- and middle-income countries (LMICs) when compared with the general population. Access to appropriate interventions is crucial for better management of malnutrition and nutritional outcomes of those children. We aimed to review the existing evidence on nutrition interventions for children with CP in LMICs. Methods: Online databases, i.e., PubMed and Scopus, and Google Scholar were searched up to 10 January 2022, to identify peer-reviewed publications/evidence on LMIC focused nutritional management guidelines/interventions. Following title screening and abstract review, full articles that met the inclusion/exclusion criteria were retained for data charting. Information about the study characteristics, nutrition interventions, and their effectiveness were extracted. Descriptive data were reported. Results: Eight articles published between 2008 and 2019 were included with data from a total of n = 252 children with CP (age range: 1 y 0 m–18 y 7 m, 42% female). Five studies followed experimental design; n = 6 were conducted in hospital/clinic/center-based settings. Four studies focused on parental/caregiver training; n = 2 studies had surgical interventions (i.e., gastrostomy) and n = 1 provided neurodevelopmental therapy feeding intervention. Dietary modification as an intervention (or component) was reported in n = 5 studies and had better effect on the nutritional outcomes of children with CP compared to interventions focused on feeding skills or other behavioral modifications. Surgical interventions improved nutritional outcomes in both studies; however, none documented any adverse consequences of the surgical interventions. Conclusion: There is a substantial knowledge gap on nutrition interventions for children with CP in LMICs. This hinders the development of best practice guidelines for the nutritional management of children with CP in those settings. Findings suggest interventions directly related to growth/feeding of children had a better outcome than behavioral interventions. This should be considered in planning of nutrition-focused intervention or comprehensive services for children with CP in LMICs.
Strengthening Sugar-Sweetened Beverage Taxation for Non-Communicable Disease Prevention: A Comparative Political Economy Analysis Case Study of Fiji and Tonga
Authors: Mounsey Sarah , Vaka Aspasia Katrina , Cama Tilema , Waqa Gade , McKenzie Briar , Thow Anne Marie
Published: March 2022

Diet-related fiscal policy is an effective NCD prevention strategy. However, current sugar-sweetened beverage (SSB) taxes in Fiji and Tonga have not had the desired effect; SSB consumption in Fiji, for example, contributes to mortality more than double the global rates and is highest in the WHO Western Pacific Region. We therefore aimed to better understand the perceived underlying political economy drivers that have and continue to affect change in each country. Our study design utilised a comparative case study that triangulated documentary policy and stakeholder analysis with semi-structured stakeholder interviews in both countries and an in-depth corporate political activity analysis in Fiji. We drew on theoretical frameworks relevant to political economy to collect and analyse policy and stakeholder data, and utilised established corporate political activity frameworks to analyse industry activity. Common findings to both Fiji and Tonga suggested that the SSB tax impact could be increased through multisectoral engagement, embracing a whole-of-society approach, strengthened institutional structures and leveraging off competing priorities across sectors towards more common goals. These findings provide opportunities and lessons for Fiji and Tonga as well as other similar settings seeking to strengthen or upscale the impact of diet-related fiscal policy.
Fiber Consumption Mediates Differences in Several Gut Microbes in a Subpopulation of Young Mexican Adults
Authors: Rodríguez-Lara Avilene , Plaza-Díaz Julio , López-Uriarte Patricia , Vázquez-Aguilar Alejandra , Reyes-Castillo Zyanya , Álvarez-Mercado Ana I.
Published: March 2022

Diet is a determinant for bodyweight and gut microbiota composition. Changes in dietary patterns are useful for the prevention and management of overweight and obesity. We aim to evaluate diet behavior and its potential association with selected gut bacteria and body weight among Mexican young adults. Mexican college students aged between 18 and 25 (normal-weight, overweight, and obese) were recruited. Anthropometric variables were recorded. A validated food frequency questionnaire was applied to all the participants. The percentages of macronutrients, fiber, and energy were calculated, and fecal samples were analyzed by real-time-qPCR to quantify selected gut bacteria. All the participants showed an unbalanced dietary pattern. However, the consumption of fruits, non-fat cereals, and oils and fats without protein were higher in the normal-weight individuals. In the overweight/obese participants, fiber intake did not correlate with the microbial variables, while Kcal from protein and Clostridium leptum correlated positively with Lactobacillus. Similarly, Clostridium coccoides-Eubacterium rectale correlated with Akkermansia muciniphila. In the normal-weight participants, Clostridium leptum and Lactobacillus correlated positively with Clostridium coccoides-Eubacterium rectale and Bifidobacterium, respectively, and Bacteroidetes negatively with Akkermansia muciniphila. In conclusion, a higher fiber intake had a positive impact on body weight and bacterial gut composition in this Mexican population of college students.
The Outer Membrane Vesicles of Salmonella enterica Serovar Typhimurium Activate Chicken Immune Cells through Lipopolysaccharides and Membrane Proteins
Authors: Cui Hongxiao , Sun Yajun , Lin Hua , Zhao Yan , Zhao Xin
Published: March 2022

Salmonella is a common pathogen which can secrete outer membrane vesicles (OMVs). However, the effect of OMVs from Salmonella enterica Serovar Typhimurium (S. Typhimurium) of poultry origin on cells of the chicken innate immune system is not well known. In this study, S. Typhimurium OMVs were first isolated from three different poultry strains of Salmonella, Salmonella CVCC542, SALA, and SALB. In order to investigate the effect of OMVs on the maturation of monocytes into macrophages, both bone marrow-derived (BMD) monocytes and macrophage cell line HD11 cells were used. OMVs promoted the formation of monocyte dendrites in both types of cells, enabled BMD cells to become larger, and stimulated expression of LPS-induced TNF-αfactor (LITAF), IL-6, and inducible nitric oxide synthase (iNOS) genes in HD11 cells. These results demonstrated the capability of OMVs to promote the development of chicken monocytes into macrophages and the maturation of macrophages. In order to study the effect of OMVs on the phagocytosis of macrophages, chicken spleen-derived monocytes and HD11 cells were used. Phagocytosis of FITC-Salmonella and FITC-dextran by these two types of cells was enhanced after stimulation with OMVs. To determine which components in OMVs were responsible for the above observed results, OMVs were treated with proteinase K(PK) or polymyxin B (PMB). Both treatments reduced the phagocytosis of FITC-Salmonella by HD11 cells and chicken spleen mononuclear cells and reduced the secretion of IL-1β, LITAF, and IL-6 cytokines. These results demonstrated that Salmonella OMVs activated chicken macrophages and spleen mononuclear cells and the activation was achieved mainly through lipopolysaccharides and membrane proteins.
Occurrence and Distribution of Fusarium Communities in the Root Zone in a Post-Bog Permanent Meadow in Relation to Mineral Fertilization and Growing Seasons
Authors: Korniłłowicz-Kowalska Teresa , Wojdyło-Kotwica Bernadeta , Bohacz Justyna , Możejko Michał
Published: March 2022

The present study is the first report of a detailed analysis of the frequency of Fusarium and genera related to Fusarium colonizing the root zone of clovers and grasses growing in a permanent meadow established on peat-muck soil in a post-bog habitat. The isolation of fungi was carried out on the Nash and Snyder medium with the plate dilution method. The taxonomic identification of the collection of pure fungal cultures was based on morphological features revealed by macroscopic and microscopic observations. The species dominance coefficients, Marczewski–Steinhaus and Simpson species diversity index were calculated. Eight Fusarium complexes were distinguished. The distribution of the Fusarium population was uneven, which was generally reflected in a higher frequency of the F. oxysporum species complex in the clover root zone and M. nivale, F. avenaceum from the Fusarium tricinctum species complex, and F. culmorum from the F. sambucinum species complex in the grass root zone. The highest similarity of fungi was determined in the rhizoplane and the endorhizosphere. The highest species diversity and the highest population size were determined in the rhizosphere soil. The fertilization treatment reduced the growth rates in the Fusarium sensu lato and in genera related to Fusarium, as evidenced by the decrease in the total abundance and species richness. The root colonization by the Fusarium, especially the F. oxysporum species complex, was not accompanied by plant pathologies, which suggests a saprotrophic and endophytic rather than parasitic character of the relationships with the plant host.
Type Strains of Entomopathogenic Nematode-Symbiotic Bacterium Species, Xenorhabdus szentirmaii (EMC) and X. budapestensis (EMA), Are Exceptional Sources of Non-Ribosomal Templated, Large-Target-Spectral, Thermotolerant-Antimicrobial Peptides (by Both), and Iodinin (by EMC)
Authors: Fodor András , Gualtieri Maxime , Zeller Matthias , Tarasco Eustachio , Klein Michael G. , Fodor Andrea M. , Haynes Leroy , Lengyel Katalin , Forst Steven A. , Furgani Ghazala M. , Karaffa Levente , Vellai Tibor
Published: March 2022

Antimicrobial multidrug resistance (MDR) is a global challenge, not only for public health, but also for sustainable agriculture. Antibiotics used in humans should be ruled out for use in veterinary or agricultural settings. Applying antimicrobial peptide (AMP) molecules, produced by soil-born organisms for protecting (soil-born) plants, seems a preferable alternative. The natural role of peptide-antimicrobials, produced by the prokaryotic partner of entomopathogenic-nematode/bacterium (EPN/EPB) symbiotic associations, is to sustain monoxenic conditions for the EPB in the gut of the semi-anabiotic infective dauer juvenile (IJ) EPN. They keep pathobiome conditions balanced for the EPN/EPB complex in polyxenic (soil, vanquished insect cadaver) niches. Xenorhabdus szentirmaii DSM16338(T) (EMC), and X. budapestensis DSM16342(T) (EMA), are the respective natural symbionts of EPN species Steinernema rarum and S. bicornutum. We identified and characterized both of these 15 years ago. The functional annotation of the draft genome of EMC revealed 71 genes encoding non-ribosomal peptide synthases, and polyketide synthases. The large spatial Xenorhabdus AMP (fabclavine), was discovered in EMA, and its biosynthetic pathway in EMC. The AMPs produced by EMA and EMC are promising candidates for controlling MDR prokaryotic and eukaryotic pathogens (bacteria, oomycetes, fungi, protozoa). EMC releases large quantity of iodinin (1,6-dihydroxyphenazine 5,10-dioxide) in a water-soluble form into the media, where it condenses to form spectacular water-insoluble, macroscopic crystals. This review evaluates the scientific impact of international research on EMA and EMC.
In Vitro Comparative Study of Platelets Treated with Two Pathogen-Inactivation Methods to Extend Shelf Life to 7 Days
Authors: Malvaux Nicolas , Defraigne Fanette , Bartziali Styliani , Bellora Camille , Mommaerts Kathleen , Betsou Fay , Schuhmacher Anne
Published: March 2022

Background and Objectives: Since 2015, platelet products have been pathogen-inactivated (PI) at the Luxemburgish Red Cross (LRC) using Riboflavin and UV light (RF-PI). As the LRC should respond to hospital needs at any time, platelet production exceeds the demand, generating a discard rate of 18%. To reduce this, we consider the extension of storage time from 5 to 7 days. This study’s objective was to evaluate the in vitro 7-day platelet-storage quality, comparing two PI technologies, RF-PI and amotosalen/UVA light (AM-PI), for platelet pools from whole-blood donations (PPCs) and apheresis platelets collected from single apheresis donation (APCs). Materials and Methods: For each product type, 6 double-platelet concentrates were prepared and divided into 2 units; one was treated with RF-PI and the other by AM-PI. In vitro platelet-quality parameters were tested pre- and post-PI, at days 5 and 7. Results: Treatment and storage lesions were observed in PPCs and APCs with both PI methods. We found a higher rate of lactate increase and glucose depletion, suggesting a stronger stimulation of the glycolytic pathway, a higher Annexin V binding, and a loss of swirling in the RF-PI-treated units from day 5. The platelet loss was significantly higher in the AM-PI compared with the RF-PI units. Conclusions: Results suggest that RF-PI treatment has a higher deleterious impact on in vitro platelet quality compared to AM-PI, but we observed higher loss of platelets with AM-PI due to the post-illumination amotosalen adsorption step. If 7-day storage is needed, it can only be achieved with AM-PI, based on our quality criteria.
Antimicrobial Activity of Pinus wallachiana Leaf Extracts against Fusarium oxysporum f. sp. cubense and Analysis of Its Fractions by HPLC
Authors: Ain Qurat Ul , Asad Shahzad , Ahad Karam , Safdar Muhammad Naeem , Jamal Atif
Published: March 2022

Fusarium wilt has ruined banana production and poses a major threat to its industry because of highly virulent Fusarium oxysporum f. sp. cubense (Foc) race 4. The present study focused on the efficacy of Pinus wallachiana leaf extracts and its organic fractions against Foc in in vitro and greenhouse experiments. The presence of polyphenols in the fractions was also investigated using high performance liquid chromatography (HPLC). The in vitro tests carried out for the leaf extract of P. wallachiana showed its inhibitory effect on the mycelial growth and, based on this evidence, further characterization of fractions were done. Complete mycelial inhibition and the highest zone of inhibition against Foc was observed for the n-butanol fraction in vitro, while the n-hexane and dichloromethane fractions showed lower disease severity index (DSI) in greenhouse experiments. The fractions were further analysed by HPLC using nine polyphenolic standards, namely quercitin, myrecitin, kaempferol, rutin, gallic acid, trans-ferulic acid, coumeric acid, epicatechin and catechin. The highest content of polyphenols, based on standards used, was quantified in the n-butanol fraction followed by the ethyl acetate fraction of the leaf extract. This is the first report of antimicrobial activity of Pinus wallachiana extracts against Foc to the best of our knowledge.
Ingrowing Liver as Atypical Recurrent Diaphragmatic Hernia Presentation—Diagnostic and Treatment Difficulties: A Case Report
Authors: Borselle Dominika , Międzybrodzki Krzysztof , Gerus Sylwester , Zaleska-Dorobisz Urszula , Hałoń Agnieszka , Szenborn Leszek , Patkowski Dariusz
Published: March 2022

(1) Introduction: Recurrent diaphragmatic hernia is a relevant diagnostic and treatment dilemma. We have presented a patient with ingrowing liver as an atypical diaphragmatic hernia recurrence and discussed major aspects of diagnostic methods and the selection of an appropriate operative treatment. (2) Case description: We discuss a case of a patient with right-sided recurrent CDH (Congenital Diaphragmatic Hernia) who had primary thoracoscopic repair in newborn period. During infancy and early childhood, the patient presented recurrent upper and lower respiratory tract infections and bronchial hyperreactivity. The clinical picture was initially unclear. A CT scan was inconclusive to diagnose a recurrence. The patient was scheduled to have a re-thoracoscopy. A part of the liver was herniated into the pleural cavity. This fragment of ‘ingrowing’ liver was removed, and the diaphragmatic secondary defect was repaired. (3) Conclusions: This case proved that thoracoscopy can be a preferred technique in the diagnosis and treatment of CDH recurrence.
ApoA-I Nanoparticles as Curcumin Carriers for Cerebral Endothelial Cells: Improved Cytoprotective Effects against Methylglyoxal
Authors: Narra Sai Sandhya , Rosanaly Sarah , Rondeau Philippe , Patche Jessica , Veeren Bryan , Gonthier Marie-Paule , Viranaicken Wildriss , Diotel Nicolas , Ravanan Palaniyandi , Hellencourt Christian Lefebvre d’ , Meilhac Olivier
Published: March 2022

Methylglyoxal (MGO) is a highly reactive metabolite of glucose present at elevated levels in diabetic patients. Its cytotoxicity is associated with endothelial dysfunction, which plays a role in cardiovascular and cerebrovascular complications. Although curcumin has many therapeutic benefits, these are limited due to its low bioavailability. We aimed to improve the bioavailability of curcumin and evaluate a potential synergistic effect of curcumin and reconstituted high-density lipoprotein (rHDL) nanoparticles (Cur-rHDLs) on MGO-induced cytotoxicity and oxidative stress in murine cerebrovascular endothelial cells (bEnd.3). Cur-rHDL nanoparticles (14.02 ± 0.95 nm) prepared by ultracentrifugation and containing curcumin were quantified by LC–MS/MS. The synergistic effect of cur-rHDL nanoparticles was tested on bEnd.3 cytotoxicity, reactive oxygen species (ROS) production, chromatin condensation, endoplasmic reticulum (ER) stress, and endothelial barrier integrity by impedancemetry. The uptake of curcumin, alone or associated with HDLs, was also assessed by mass spectrometry. Pretreatment with Cur-rHDLs followed by incubation with MGO showed a protective effect on MGO-induced cytotoxicity and chromatin condensation, as well as a strong protective effect on ROS production, endothelial cell barrier integrity, and ER stress. These results suggest that Cur-rHDLs could be used as a potential therapeutic agent to limit MGO-induced dysfunction in cerebrovascular endothelial cells by enhancing the bioavailability and protective effects of curcumin.
Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines
Authors: Zaki Randa Mohammed , Alfadhel Munerah M. , Alshahrani Saad M. , Alsaqr Ahmed , Al-Kharashi Layla A. , Anwer Md Khalid
Published: March 2022

The purpose of the current study was to develop Brigatinib (BGT)-loaded nanospanlastics (BGT-loaded NSPs) (S1-S13) containing Span 60 with different edge activators (Tween 80 and Pluronic F127) and optimized based on the vesicle size, zeta potential (ZP), and percent entrapment efficiency (%EE) using Design-Expert® software. The optimum formula was recommended with desirability of 0.819 and composed of Span-60:Tween 80 at a ratio of 4:1 and 10 min as a sonication time (S13). It showed predicted EE% (81.58%), vesicle size (386.55 nm), and ZP (−29.51 mv). The optimized nanospanlastics (S13) was further coated with chitosan and further evaluated for Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro release, Transmission Electron Microscopy (TEM), stability and in-vitro cytotoxicity studies against H-1975 lung cancer cell lines. The DSC and XRD revealed complete encapsulation of the drug. TEM imagery revealed spherical nanovesicles with a smooth surface. Also, the coated formula showed high stability for three months in two different conditions. Moreover, it resulted in improved and sustained drug release than free BGT suspension and exhibited Higuchi kinetic release mechanism. The cytotoxic activity of BGT-loaded SPs (S13) was enhanced three times in comparison to free the BGT drug against the H-1975 cell lines. Overall, these results confirmed that BGT-loaded SPs could be a promising nanocarrier to improve the anticancer efficacy of BGT.
Recent Advances in the Application of Mesenchymal Stem Cell-Derived Exosomes for Cardiovascular and Neurodegenerative Disease Therapies
Authors: Yang Zhimin , Li Yanyu , Wang Zihua
Published: March 2022

Exosomes are naturally occurring nanoscale vesicles that are released and received by almost all cells in the body. Exosomes can be transferred between cells and contain various molecular constitutes closely related to their origin and function, including proteins, lipids, and RNAs. The importance of exosomes in cellular communication makes them important vectors for delivering a variety of drugs throughout the body. Exosomes are ubiquitous in the circulatory system and can reach the site of injury or disease through a variety of biological barriers. Due to its unique structure and rich inclusions, it can be used for the diagnosis and treatment of diseases. Mesenchymal stem-cell-derived exosomes (MSCs-Exo) inherit the physiological functions of MSCs, including repairing and regenerating tissues, suppressing inflammatory responses, and regulating the body’s immunity; therefore, MSCs-Exo can be used as a natural drug delivery carrier with therapeutic effects, and has been increasingly used in the treatment of cardiovascular diseases and neurodegenerative diseases. Here, we summarize the research progress of MSCs-Exo as drug delivery vectors and their application for various drug deliveries, providing ideas and references for the study of MSCs-Exo in recent years.
A Novel Deep Neural Network Technique for Drug–Target Interaction
Authors: de Souza Jackson G. , Fernandes Marcelo A. C. , de Melo Barbosa Raquel
Published: March 2022

Drug discovery (DD) is a time-consuming and expensive process. Thus, the industry employs strategies such as drug repositioning and drug repurposing, which allows the application of already approved drugs to treat a different disease, as occurred in the first months of 2020, during the COVID-19 pandemic. The prediction of drug–target interactions is an essential part of the DD process because it can accelerate it and reduce the required costs. DTI prediction performed in silico have used approaches based on molecular docking simulations, including similarity-based and network- and graph-based ones. This paper presents MPS2IT-DTI, a DTI prediction model obtained from research conducted in the following steps: the definition of a new method for encoding molecule and protein sequences onto images; the definition of a deep-learning approach based on a convolutional neural network in order to create a new method for DTI prediction. Training results conducted with the Davis and KIBA datasets show that MPS2IT-DTI is viable compared to other state-of-the-art (SOTA) approaches in terms of performance and complexity of the neural network model. With the Davis dataset, we obtained 0.876 for the concordance index and 0.276 for the MSE; with the KIBA dataset, we obtained 0.836 and 0.226 for the concordance index and the MSE, respectively. Moreover, the MPS2IT-DTI model represents molecule and protein sequences as images, instead of treating them as an NLP task, and as such, does not employ an embedding layer, which is present in other models.
Safety and Pharmacokinetic Assessment of Oral Proglumide in Those with Hepatic Impairment
Authors: Hsu Christine C. , Bansal Sunil , Cao Hong , Smith Coleman I. , He Aiwu Ruth , Gay Martha D. , Li Yaoxiang , Cheema Amrita , Smith Jill P.
Published: March 2022

Proglumide is an orally administered cholecystokinin receptor antagonist that was found to improve nonalcoholic steatohepatitis, reverse liver fibrosis, and decrease incidence of hepatocellular carcinoma (HCC) in animal models. The current investigation aimed to test the pharmacokinetics and safety of proglumide in subjects with hepatic impairment compared with healthy controls. In this translational study, subjects with confirmed cirrhosis, Child-Pugh stage A or B, or healthy controls were recruited for a single-dosing study. Baseline urine and blood samples were obtained before administration of proglumide and also collected after ingestion up to 24 h. Drug concentrations measured by mass spectroscopy revealed peak plasma concentrations (Cmax) of 7847, 9721, and 10,635 ng/mL at about 1 h (Tmax) for healthy controls, subjects with Child-Pugh A, and B cirrhosis, respectively. The serum elimination half time was 3 h. Maximum urine drug concentration (Cmax = ~411 µg/mL) was observed at 3 h, and urinary drug concentration declined at 5 h. There were no adverse events reported, and follow-up liver panels in cirrhosis subjects were unchanged or improved. This investigation demonstrated that proglumide is safe and has similar pharmacokinetic properties in subjects with cirrhosis as in healthy controls; therefore, it will be safe to test the efficacy of proglumide as a therapeutic agent in those subjects with cirrhosis or HCC.
Mass Cytometry Exploration of Immunomodulatory Responses of Human Immune Cells Exposed to Silver Nanoparticles
Authors: Bae Jiwon , Ha My , Perumalsamy Haribalan , Lee Yangsoon , Song Jaewoo , Yoon Tae-Hyun
Published: March 2022

Increasing production and application of silver nanoparticles (Ag NPs) have raised concerns on their possible adverse effects on human health. However, a comprehensive understanding of their effects on biological systems, especially immunomodulatory responses involving various immune cell types and biomolecules (e.g., cytokines and chemokines), is still incomplete. In this study, a single-cell-based, high-dimensional mass cytometry approach is used to investigate the immunomodulatory responses of Ag NPs using human peripheral blood mononuclear cells (hPBMCs) exposed to poly-vinyl-pyrrolidone (PVP)-coated Ag NPs of different core sizes (i.e., 10-, 20-, and 40-nm). Although there were no severe cytotoxic effects observed, PVPAg10 and PVPAg20 were excessively found in monocytes and dendritic cells, while PVPAg40 displayed more affinity with B cells and natural killer cells, thereby triggering the release of proinflammatory cytokines such as IL-2, IL-17A, IL-17F, MIP1β, TNFα, and IFNγ. Our findings indicate that under the exposure conditions tested in this study, Ag NPs only triggered the inflammatory responses in a size-dependent manner rather than induce cytotoxicity in hPBMCs. Our study provides an appropriate ex vivo model to better understand the human immune responses against Ag NP at a single-cell level, which can contribute to the development of targeted drug delivery, vaccine developments, and cancer radiotherapy treatments.
Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters
Authors: Karimi-Jafari Maryam , Ziaee Ahmad , O’Reilly Emmet , Croker Denise , Walker Gavin
Published: March 2022

The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to explore the feasibility of cocrystallization. Ciprofloxacin (CIP) and isonicotinic acid (INCA) were selected as the model API and coformer. CIP–INCA cocrystal was produced in all techniques. It was revealed that higher cocrystal content could be achieved at longer durations of grinding and ball milling. However, milling for more than 10 min led to increased co-amorphous content instead of cocrystal. A design of experiment (DoE) approach was used for deciphering the complex correlation of screw configuration, screw speed, and temperature as HME process parameters and their respective effect on final relative cocrystal yield. Statistical analysis showed that screw configuration, temperature, and their interaction were the most critical factors affecting cocrystallization. Interestingly, screw speed had minimal impact on the relative cocrystallization yield. Cocrystallization led to increased dissolution rate of CIP in phosphate buffer up to 2.5-fold. Overall, this study shed a light on the potential of mechanochemical synthesis techniques with special focus on HME as a continuous process for producing cocrystals.
Conserved and Diverse Transcriptional Reprogramming Triggered by the Establishment of Symbioses in Tomato Roots Forming Arum-Type and Paris-Type Arbuscular Mycorrhizae
Authors: Tominaga Takaya , Yao Luxi , Saito Hikaru , Kaminaka Hironori
Published: March 2022

Arbuscular mycorrhizal (AM) fungi allocate mineral nutrients to their host plants, and the hosts supply carbohydrates and lipids to the fungal symbionts in return. The morphotypes of intraradical hyphae are primarily determined on the plant side into Arum- and Paris-type AMs. As an exception, Solanum lycopersicum (tomato) forms both types of AMs depending on the fungal species. Previously, we have shown the existence of diverse regulatory mechanisms in Arum- and Paris-type AM symbioses in response to gibberellin (GA) among different host species. However, due to the design of the study, it remained possible that the use of different plant species influenced the results. Here, we used tomato plants to compare the transcriptional responses during Arum- and Paris-type AM symbioses in a single plant species. The tomato plants inoculated with Rhizophagus irregularis or Gigaspora margarita exhibited Arum- and Paris-type AMs, respectively, and demonstrated similar colonization rates and shoot biomass. Comparative transcriptomics showed shared expression patterns of AM-related genes in tomato roots upon each fungal infection. On the contrary, the defense response and GA biosynthetic process was transcriptionally upregulated during Paris-type AM symbiosis. Thus, both shared and different transcriptional reprogramming function in establishing Arum- and Paris-type AM symbioses in tomato plants.
Features of Profiles of Biologically Active Compounds of Primary and Secondary Metabolism of Lines from VIR Flax Genetic Collection, Contrasting in Size and Color of Seeds
Authors: Porokhovinova Elizaveta A. , Shelenga Tatyana V. , Kerv Yulia A. , Khoreva Valentina I. , Konarev Alexey V. , Yakusheva Tamara V. , Pavlov Andrey V. , Slobodkina Anastasia A. , Brutch Nina B.
Published: March 2022

Flax is one of the oldest oil crops, but only since the end of the twentieth century nutritional use of its whole seeds and flour has been resumed. This crop has been evaluated for its oil fatty acid composition, content of sterols and tocopherols, carbohydrate composition of mucilage, but a comprehensive study has never been carried out, so the aim of the work was to identify differences in the metabolomic profiles of flax lines contrasting in color and size of seeds. The biochemical composition of seeds from 16 lines of the sixth generation of inbreeding was tested using gas chromatography coupled with mass spectrometry. In total, more than 90 compounds related to sugars (78% of the identified substances), free fatty acids (13%), polyatomic alcohols (5%), heterocyclic compounds, free amino acids, phytosterols and organic acids (no more than 2.5% in total) were identified. Statistical analyses revealed six main factors. The first is a factor of sugar content; the second one affects most of organic acids, as well as some free fatty acids, not related to reserve ones, the third factor is related to compounds that play a certain role in the formation of “storage” substances and resistance to stress, the fourth factor is influencing free polar amino acids, some organic and free fatty acids, the fifth one is a factor of phenolic compounds, the sixth factor combined substances not included in the first five groups. Factor analysis made it possible to differentiate all 16 lines, 10 of which occupied a separate position by one or two factors. Interestingly, the first two factors with the highest loads (20 and 15% of the total variability, respectively) showed a separate position of the gc-432 line, which differed from the others, not only by chemical composition, but also by the phenotype of the seeds, while gc-159 differed from the rest ones by the complex of organic acids and other substances taking about 1% of the extracted substances of the seed. Thus, the analysis of metabolomic profiles is promising for a comprehensive assessment of the VIR flax genetic collection, which has wide biochemical diversity.
Tobacco Plant Growth-Promoting and Antifungal Activities of Three Endophytic Yeast Strains
Authors: Petkova Mariana , Petrova Slaveya , Spasova-Apostolova Velichka , Naydenov Mladen
Published: March 2022

In this research, the biosynthetic and biocontrol potential of endophytic yeast to improve the growth and development of tobacco has been elucidated. Three yeast strains were enriched and isolated from different plant tissues. Partial sequence analysis of ITS5-5.8-ITS4 region of the nuclear ribosomal DNA with universal primers identified YD5, YE1, and YSW1 as Saccharomyces cerevisiae (S. cerevisiae), Zygosaccharomyces bailii (Z. bailii), and Saccharomyces kudriavzevii (S. kudriavzevii), respectively. When cultivated in a medium supplemented with 0.1% L-tryptophan, isolated yeast strains produced indole-3-acetic acid (IAA). The capacities of those strains to improve the mobility of phosphorus and synthesize siderophores has been proven. Their antimicrobial activities against several Solanaceae plant pathogenic fungi (Alternaria solani pathovar. tobacco, Rhizoctonia solani, and Fusarium solani pathovar. phaseoli) were determined. S. cerevisiae YD5, Z. bailii YE1, and S. kudriavzevii YSW1 inhibited the growth of all tested pathogens. Yeast strains were tested for endophytic colonization of tobacco by two different inoculation methods: soil drench (SD) and leaf spraying (LS). To establish colonization in the various tissues of tested tobacco (Nicotiana tabaccum L.) plants, samples were taken on the seventh, fourteenth, and twenty-first days after treatment (DAT), and explants were inoculated on yeast malt agar (YMA). Both techniques of inoculation showed a high frequency of colonization from 83.33% to 100%. To determine the effectiveness of the microbial endophytes, their effect on some physiological processes in the plant were analyzed, such as photosynthesis, stomatal conductivity, and transpiration intensity. The effect of single and double treatment with yeast inoculum on the development and biochemical parameters of tobacco was reported. Plants have the ability of structural and functional adaptation to stress effects of different natures. All treated plants had a higher content of photosynthetic pigments compared to the control. Photosynthesis is probably more intense, and growth stimulation has been observed. The chlorophyll a/b ratio remained similar, and the total chlorophyll/carotenoid ratio slightly increased as a result of elevated chlorophyll levels. The most significant stimulating effect was recorded in tobacco plants treated by foliar spraying with Z. bailii YE1 and S. cerevisiae YD5. In contrast, S. kudriavzevii YSW1 had a better effect when applied as a soil drench. Thus, S. cerevisiae YD5, Z. bailii YE1, and S. kudriavzevii YSW1 have a high potential to be used as a biocontrol agents in organic agriculture.
Metabolite Profiles Provide Insights into Underlying Mechanism in Bupleurum (Apiaceae) in Response to Three Levels of Phosphorus Fertilization
Authors: Sun Jialin , Duan Zejia , Zhang Ye , Cao Sisi , Tang Zhonghua , Abozeid Ann
Published: March 2022

Phosphorus (P) deficiency affects plant yield and quality, yet at the same time, excessive phosphorus application does not necessarily promote the growth of plants. How to maintain a balance between biomass accumulation and phosphorus application is a problem. Therefore, the purpose of this research was to explore the relationship between yield and quality of Bupleurum and phosphorus fertilization, based on three phosphorus fertilization levels (20 kg∙ha−1; 10 kg∙ha−1; and 0 kg∙ha−1). We adopted gas chromatography-mass spectrometry to assess the response of primary metabolites of different plant tissues (flowers, main shoots, lateral shoots and roots) to phosphorus fertilization. At the same time, high-performance liquid chromatography was used to quantify saikosaponin A and saikosaponin D, the main active ingredients of Bupleurum. Our research showed that low phosphorus level application has a positive impact on the yield and quality of Bupleurum, especially the above-ground parts increasing the fresh weight of flowers and lateral shoots and the length of main shoots, and moreover, increasing the saikosaponins content in all above-ground parts while decreasing the content in roots which show no significance increase in fresh weight and length. However, high phosphorus level showed a negative impact as it decreases the saikosaponins content significantly in flowers and roots. Furthermore, phosphorus application changed the proportion of saikosaponins, promoting the content of saikosaponin A and inhibiting the content of saikosaponin D in most organs of Bupleurum. Therefore, we can say that high phosphorus application is not preferable to the yield and quality of Bupleurum. To identify the metabolic pathways and special key metabolites, a total of 73 metabolites were discovered, and four differential metabolites—ether, glycerol, chlorogenic and L-rhamnose—were considered to be the key metabolites of Bupleurum’s response to phosphorus fertilization. Furthermore, Bupleurum’s response to phosphorus fertilization was mainly related to metabolic pathways, such as starch and sucrose metabolism and galactose metabolism. Under the phosphorus level, the content of sugars, organic acids and their derivatives, polyols and their derivatives and alkyl were upregulated in flowers. Furthermore, the contents of compounds in the main shoot and lateral shoots showed the same upward trend, except glycosides and polyols and their derivatives.
Vegetation Dynamics in a Loess Grassland: Plant Traits Indicate Stability Based on Species Presence, but Directional Change When Cover Is Considered
Authors: Csontos Péter , Tamás Júlia , Kovács Zsófia , Schellenberger Judit , Penksza Károly , Szili-Kovács Tibor , Kalapos Tibor
Published: March 2022

This article evaluates the three-year vegetation dynamics of a species rich, protected steppe grassland on loess where no grazing occurred for decades at Bicske, Central Hungary. A detailed coenological survey of vascular vegetation was conducted in four permanent plots of 16 m2 each from 2018 to 2020. Raunkiaer’s life-forms, distribution range, and thousand-seed weight of species were evaluated. Shannon diversity and turnover rates for the species and the vegetation were also determined for each plot. In total, 108 vascular plant species were detected. The results indicate grassland stability when plant traits spectra were based on species presence data, but directional change if species cover values were used to weight trait categories. During the three years of the study, chamaephytes decreased and woody species increased their contribution for the Raunkiaer’s life-forms, while the cosmopolitan group has steadily lost its significance for distribution range types. Shannon diversity varied between 2.46 and 3.18 among plots (based on natural logarithm) and remained statistically unchanged through time. Average species turnover rates were 14.18% for 2018/19 and 17.52% for 2019/20, whereas corresponding values for vegetation turnover rates were 25.83% and 23.28%. Vegetation turnover rate was significantly higher than the species turnover rate.
Triterpenes and Phenolic Compounds from Euphorbia deightonii with Antiviral Activity against Herpes Simplex Virus Type-2
Authors: Saidu Muhammad Bello , Kúsz Norbert , Tsai Yu-Chi , Vágvölgyi Máté , Berkecz Róbert , Kókai Dávid , Burián Katalin , Hohmann Judit , Rédei Dóra
Published: March 2022

Two undescribed compounds, 3β,7β-dihydroxy-24-methylenelanosta-8-ene-11-one (1) and neolignane deightonin (4) were isolated from the aerial parts of Euphorbia deightonii Croizat together with six known compounds, namely, kansenone (2), euphorbol-7-one (3), dehydrodiconiferyl diacetate (5), marylaurencinol D (6), scoparon (7), and 3,4,3′-tri-O-methylellagic acid (8). The structures of the isolated compounds were determined by HRESIMS, 1D (1H, 13C JMOD) and 2D NMR (HSQC, HMBC, 1H–1H COSY, NOESY) spectroscopic analysis, and by comparison of the assignments with literature data. The anti-herpes simplex virus type-2 activity of the isolated compounds were investigated by qRT-PCR assay on Vero cells after determining cytotoxic concentration 50% (CC50). Compounds 1, 3, 4, and 7 exhibited inhibitory effects with respective IC50 values of 7.05, 2.42, 11.73, and 0.032 µM. Scoparon (7) showed the strongest anti-HSV activity with a selectivity index of 10.93.