bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of FTO Genetic Variants on Obesity and Its Metabolic Consequences is Dependent on Daily Macronutrient Intake
Authors: Czajkowski Przemyslaw , Adamska-Patruno Edyta , Bauer Witold , Fiedorczuk Joanna , Krasowska Urszula , Moroz Monika , Gorska Maria , Kretowski Adam
Published: October 2020

Numerous studies have identified the various fat mass and obesity-associated (FTO) genetic variants associated with obesity and its metabolic consequences; however, the impact of dietary factors on these associations remains unclear. The aim of this study was to evaluate the association between FTO single nucleotide polymorphisms (SNPs), daily macronutrient intake, and obesity and its metabolic consequences. From 1549 Caucasian subjects of Polish origin, genotyped for the FTO SNPs (rs3751812, rs8044769, rs8050136, and rs9939609), 819 subjects were selected for gene–diet interaction analysis. Anthropometric measurements were performed and total body fat content and distribution, blood glucose and insulin concentration during oral glucose tolerance test (OGTT), and lipid profile were determined. Macronutrient intake was analyzed based on three-day food records, and daily physical activity levels were evaluated using the International Physical Activity Questionnaire Long Form (IPAQ-LF). Our study shows that carriers of the GG genotype of rs3751812 presented lower body weight, body mass index (BMI), total body fat content, and hip and waist circumference and presented lower obesity-related markers if more than 48% of daily energy intake was derived from carbohydrates and lower subcutaneous and visceral fat content when energy intake derived from dietary fat did not exceed 30%. Similar results were observed for rs8050136 CC genotype carriers. We did not notice any significant differences in obesity markers between genotypes of rs8044769, but we did observe a significant impact of diet-gene associations. Body weight and BMI were significantly higher in TT and CT genotype carriers if daily energy intake derived from carbohydrates was less than 48%. Moreover, in TT genotype carriers, we observed higher blood glucose concentration while fasting and during the OGTT test if more than 18% of total energy intake was derived from proteins. In conclusion, our results indicate that daily macronutrient intake may modulate the impact of FTO genetic SNPs on obesity and obesity-related metabolic consequences.
Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life
Authors: Kim Jae Geun , Lee Byung Ju , Jeong Jin Kwon
Published: October 2020

Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.
Reformulation of Packaged Foods and Beverages in the Colombian Food Supply
Authors: Lowery Caitlin M. , Mora-Plazas Mercedes , Gómez Luis Fernando , Popkin Barry , Taillie Lindsey Smith
Published: October 2020

Public discussion, advocacy, and legislative consideration of policies aimed at reducing consumption of processed foods, such as sugar-sweetened beverage (SSB) taxes and mandatory front-of-package (FOP) warning labels, may stimulate product reformulation as a strategy to prevent regulation. In Colombia, there have been major legislative pushes for SSB taxes and FOP labels, although neither has passed to date. In light of the ongoing policy debate and successful implementation of similar policies in Peru and Chile, we explored manufacturer reformulation in the Colombian food supply. We compared the quantities of nutrients of concern (including sugar, sodium, and saturated fat) from the nutrition facts panels of the same 102 packaged foods and 36 beverages from the top-selling brands in Colombia between 2016 and 2018. Our analyses showed a substantial decrease in median sugar content of beverages, from 9.2 g per 100 mL to 5.2 g per 100 mL, and an increase in the percentage of beverages containing non-nutritive sweeteners (NNS), from 33% to 64% (p = 0.003). No meaningful changes in the quantities of nutrients of concern among foods were observed. Our findings suggest little reformulation has occurred in Colombia in the absence of mandatory policies, except for the substitution of sugar with NNS among beverages.
Cellular Function of Annexin A1 Protein Mimetic Peptide Ac2-26 in Human Skin Keratinocytes HaCaT and Fibroblast Detroit 551 Cells
Authors: Kim Seong Min , Ha Sang Eun , Vetrivel Preethi , Kim Hun Hwan , Bhosale Pritam Bhagwan , Park Jung Eun , Heo Jeong Doo , Kim Young Sil , Kim Gon Sup
Published: October 2020

Inflammation of the skin is the most common dermatological problem in human. The anti-inflammatory mediated responses of the skin cells provide a mechanism for combating these conditions. Annexin A1 (AnxA1) is one of the proteins that has been shown to have a potent anti-inflammatory effect. However, the effects and mechanisms of AnxA1 in skin keratinocyte and fibroblast have not been reported yet. In the current study, we hypothesized that Ac2-26, AnxA1 mimetic peptide, ameliorates inflammation and wrinkle formation in human skin cells. Therefore, we aimed to identify whether Ac2-26 has anti-inflammatory and anti-wrinkle effects in human keratinocyte (HaCaT) and fibroblast (Detroit 551) cells, respectively. Human HaCaT cells were stimulated by TNF-α/IFN-γ with or without Ac2-26, to identify the anti-inflammatory effect. Human Detroit 551 cells were treated with Ac2-26 to verify the anti-wrinkle effect. Initially, cell cytotoxicity was carried out in each cell line treated using Ac2-26 by MTT assay. Human MDA, IL-8, and procollagen secretion were detected by ELISA assay. The inflammatory chemokines were measured by qRT-PCR analysis. To demonstrate the mechanism, MAPK, NF-κB, JAK/STAT, and MMPs were analyzed by Western blotting. As a result, we identified that Ac2-26 significantly decreased the expression of TNF-α/IFN-γ-stimulated pro-inflammatory chemokines, including IL-1β, IL-6, IL-8, MDC, TARC, and TNF-α, by inhibiting the activation of MAPK, NF-κB, and JAK/STAT pathway in TNF-α/IFN-γ-stimulated HaCaT human keratinocytes. In addition, we also identified that Ac2-26 significantly induced collagen synthesis by generating pro-collagen, and suppressed collagen degradation by inhibiting the collagenase MMP-1 and MMP-8 expression. Collectively, these results suggest that Ac2-26 shows anti-inflammatory and anti-wrinkling effect. These effects may lead to the development of preventive and therapeutic application for inflammation-related skin disease and wrinkle formation.
Beneficial Effect of Dietary Diversity on the Risk of Disability in Activities of Daily Living in Adults: A Prospective Cohort Study
Authors: Zhang Jian , Zhao Ai , Wu Wei , Ren Zhongxia , Yang Chenlu , Wang Peiyu , Zhang Yumei
Published: October 2020

Disability in activities of daily living (ADL) is common in elderly people. Dietary diversity is associated with several age-related diseases. The evidence on dietary diversity score (DDS) and ADL disability is limited. This study was based on the China Health and Nutrition Survey. Prospective data of 5004 participants were analyzed. ADL disability was defined as the inability to perform at least one of the five self-care tasks. Cox proportional regression models were conducted to estimate the association of cumulative average DDS with the risk of ADL disability. Logistic regression models were performed to estimate the odds ratios for the average DDS, the baseline DDS, and the recent DDS prior to the end of the survey in relation to ADL disability, respectively. The results indicate that higher average DDS was associated with a decreased risk of ADL disability (T3 vs. T1: hazard ratio 0.50; 95% confidence interval 0.39–0.66). The association was stronger among participants who did not had comorbidity at baseline than those who did (P-interaction 0.035). The average DDS is the most pronounced in estimating the association of DDS with ADL disability of the three approaches. In summary, higher DDS has beneficial effects on ADL disability, and long-term dietary exposure is more preferable in the investigation of DDS and ADL.
Combined Impact of a Faster Self-Reported Eating Rate and Higher Dietary Energy Intake Rate on Energy Intake and Adiposity
Authors: Teo Pey Sze , van Dam Rob M. , Forde Ciarán G.
Published: October 2020

Eating more quickly and consuming foods with a higher energy-intake-rate (EIR: kcal/min) is associated with greater energy intake and adiposity. However, it remains unclear whether individuals who eat more quickly are more likely to consume foods with higher EIR. We investigated the overlap between self-reported eating rate (SRER) and the consumption of higher EIR foods, and their combined impact on daily energy intake and adiposity in a population-based Asian cohort (n = 7011; 21–75y). Food consumption was assessed using a validated Food Frequency Questionnaire. Moderated regression with simple slope analysis was conducted to evaluate whether SRER modified the association between dietary EIR and total dietary energy intakes. Faster eaters consumed a significantly higher proportion of energy from higher EIR foods among overweight individuals, but not among normal-weight individuals. Associations between dietary EIR and total energy intake were stronger among medium (β = 15.04, 95%CI: 13.00–17.08) and fast (β = 15.69, 95%CI: 12.61–18.78) eaters, compared with slower eaters (β = 9.89, 95%CI: 5.11–14.67; p-interaction = 0.032). Higher dietary EIR also tended to be more strongly associated with BMI in fast eaters (β = 0.025, 95%CI: 0.011–0.038) than in slow eaters (β = 0.017, 95%CI: −0.007–0.040). These findings suggest that the combination of eating more quickly and selecting a greater proportion of energy from higher EIR foods (i.e., softly textured, energy dense), promoted higher dietary energy intakes and adiposity.
Cooking Frequency and Perception of Diet among US Adults Are Associated with US Healthy and Healthy Mediterranean-Style Dietary Related Classes: A Latent Class Profile Analysis
Authors: Farmer Nicole , Lee Lena J. , Powell-Wiley Tiffany M. , Wallen Gwenyth R.
Published: October 2020

Background: Meal habits are associated with overall dietary quality and favorable dietary patterns determined by the Healthy Eating Index (HEI). However, within dietary patterns, complexities of food combinations that are not apparent through composite score determination may occur. Also, explorations of these food combinations with cooking and perceived diet quality (PDQ) remain unknown. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 were utilized to determine the frequency of cooking at home and PDQ, along with sociodemographic variables. Latent class profile analysis was performed to determine person-centered data-driven analysis using the dietary index, HEI-2010, at both the daily and dinner meal-time levels. Multinomial logistic regression analysis was utilized to evaluate the association of dietary patterns with all covariates. Results: For daily HEI, five distinct dietary classes were identified. For dinner HEI, six classes were identified. In comparison to the standard American diet classes, home cooking was positively associated with daily (p < 0.05) and dinner (p < 0.001) dietary classes that had the highest amounts of total vegetable and greens/beans intake. PDQ was positively associated with these classes at the daily level (p < 0.001), but negatively associated with healthier classes at the dinner level (p < 0.001). Conclusion: The use of latent class profile analysis at the daily and dinner meal-time levels identified that food choices coalesce into diverse intakes, as shown by identified dietary classes. Home cooking frequency could be considered a positive factor associated with higher vegetable intake, particularly greens/beans, at the daily and dinner levels. At the same time, the perception of diet quality has a positive association only with daily choices.
Skeletal Muscle and the Maintenance of Vitamin D Status
Authors: Rybchyn Mark S. , Abboud Myriam , Puglisi David A. , Gordon-Thomson Clare , Brennan-Speranza Tara C. , Mason Rebecca S. , Fraser David R.
Published: October 2020

Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D), which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into the blood. This uptake and release of 25(OH)D by muscle accounts for the very long half-life of this metabolite in the circulation. Since 25(OH)D concentration in the blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain an adequate vitamin D status in winter.
Visual Function and Macular Carotenoid Changes in Eyes with Retinal Drusen—An Open Label Randomized Controlled Trial to Compare a Micronized Lipid-Based Carotenoid Liquid Supplementation and AREDS-2 Formula
Authors: Davey Pinakin Gunvant , Henderson Thomas , Lem Drake W. , Weis Rebecca , Amonoo-Monney Stephanie , Evans David W.
Published: October 2020

Purpose: To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. Methods: An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. Results: Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. Conclusion: The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).
Dietary Protein to Carbohydrate Ratio and Incidence of Metabolic Syndrome in Korean Adults Based on a Long-Term Prospective Community-Based Cohort
Authors: Paik Jean Kyung , Park Mira , Shin Ji Eun , Jang Suk-Yong , Shin Ji-Yeon
Published: October 2020

Interest in high protein diets has recently been increasing for reduction of weight or management of cardiometabolic risks. However, studies on high protein, low carbohydrate diet in Asians are limited. This study aimed to estimate whether the dietary ratio of protein (%) to carbohydrate (%) from total energy intake (p/c ratio) is associated with the risk of metabolic syndrome (MS) and its components in Korean adults using a long-term prospective cohort. A total of 6335 participants from the Korean Genome and Epidemiology Study, aged between 40 and 69 years, with no previous diagnosis of MS, cardiovascular diseases, or cancer at baseline (2001–2002) were followed until 2013. Dietary intake was measured using a validated semiquantitative food-frequency questionnaire. MS components were measured at baseline and every 2 years. During a mean of 7.7 years of follow up, 1198 (36.1%) men and 1169 (38.8%) women developed MS. The multivariate adjusted hazard ratio (HR) of incident MS was 1.43 (95% confidence interval, 1.09–1.89) for the highest compared lowest quintile of p/c ratio in men. When evaluating each component of MS, higher dietary p/c ratio was associated with an increased risk of high triglyceride and fasting glucose in men (HR for fifth vs. first quintile, 1.39 and 1.41 in Model 3, respectively). However, we observed no associations with incident MS and its components and dietary p/c ratio in women. In conclusion, we found that high dietary p/c ratio was associated with an increased risk of MS and its components (i.e., increased triglycerides and fasting glucose) in men. Our study suggested that even if the absolute amount of protein intake is not large, an increased p/c ratio may increase the risk of metabolic diseases.
Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain
Authors: Rubín-García María , Vitelli-Storelli Facundo , Molina Antonio José , Zamora-Ros Raúl , Aragonés Nuria , Adarnaz Eva , Castaño-Vinyals Gemma , Obón-Santacana Mireia , Gómez-Acebo Inés , Molina-Barceló Ana , Fernández-Tardón Guillermo , Jiménez-Moleón José J , Alguacil Juan , Chirlaque María Dolores , Toledo Estefanía , Pérez-Gómez Beatriz , Pollán Marina , Kogevinas Manolis , Martín Vicente
Published: October 2020

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from different regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed effects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32–0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36–0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28–0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34–0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39–0.80) were inversely associated with GC risk. No differences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results.
Polygenetic-Risk Scores for A Glaucoma Risk Interact with Blood Pressure, Glucose Control, and Carbohydrate Intake
Authors: Jee Donghyun , Huang ShaoKai , Kang Suna , Park Sunmin
Published: October 2020

Glaucoma, a leading cause of blindness, has multifactorial causes, including environmental and genetic factors. We evaluated genetic risk factors of glaucoma with gene-gene interaction and explored modifications of genetic risk with gene-lifestyles interaction in adults >40 years. The present study included 377 subjects with glaucoma and 47,820 subjects without glaucoma in a large-scale hospital-based cohort study from 2004 to 2013. The presence of glaucoma was evaluated by a diagnostic questionnaire evaluated by a doctor. The genome-wide association study was performed to identify genetic variants associated with glaucoma risk. Food intake was assessed using a semiquantitative food frequency questionnaire. We performed generalized multifactor dimensionality reduction analysis to construct polygenetic-risk score (PRS) and explored gene × nutrient interaction. PRS of the best model included LIM-domain binding protein-2 (LDB2) rs3763969, cyclin-dependent kinase inhibitor 2B (CDKN2B) rs523096, ABO rs2073823, phosphodiesterase-3A (PDE3A) rs12314390, and cadherin 13 (CDH13) rs12449180. Glaucoma risk in the high-PRS group was 3.02 times that in the low-PRS group after adjusting for confounding variables. For those with low serum glucose levels (<126 mg/dL), but not for those with high serum glucose levels, glaucoma risk in the high-PRS group was 3.16 times that in the low-PRS group. In those with high carbohydrate intakes (≥70%), but not in those with low carbohydrate intakes, glaucoma risk was 3.74 times higher in the high-PRS group than in the low-PRS group. The glaucoma risk was 3.87 times higher in the high-PRS group than in the low-PRS group only in a low balanced diet intake. In conclusion, glaucoma risk increased by three-fold in adults with a high PRS, and it can be reduced by good control of serum glucose concentrations and blood pressure (BP) with a balanced diet intake. These results can be applied to precision nutrition to reduce glaucoma risk.
Predictive Accuracy of COVID-19 World Health Organization (WHO) Severity Classification and Comparison with a Bayesian-Method-Based Severity Score (EPI-SCORE)
Authors: de Terwangne Christophe , Laouni Jabber , Jouffe Lionel , Lechien Jerome , Bouillon Vincent , Place Sammy , Capulzini Lucio , Machayekhi Shahram , Ceccarelli Antonia , Saussez Sven , Sorgente Antonio ,   on behalf of EPIBASE TEAM
Published: October 2020

Objectives: Assess the predictive accuracy of the WHO COVID-19 severity classification on COVID-19 hospitalized patients. The secondary aim was to compare its predictive power with a new prediction model, named COVID-19 EPI-SCORE, based on a Bayesian network analysis. Methods: We retrospectively analyzed a population of 295 COVID-19 RT-PCR positive patients hospitalized at Epicura Hospital Center, Belgium, admitted between March 1st and April 30th, 2020. Results: Our cohort’s median age was 73 (62–83) years, and the female proportion was 43%. All patients were classified following WHO severity classification at admission. In total, 125 (42.4%) were classified as Moderate, 69 (23.4%) as Severe, and 101 (34.2%) as Critical. Death proportions through these three classes were 11.2%, 33.3%, and 67.3%, respectively, and the proportions of critically ill patients (dead or needed Invasive Mechanical Ventilation) were 11.2%, 34.8%, and 83.2%, respectively. A Bayesian network analysis was used to create a model to analyze predictive accuracy of the WHO severity classification and to create the EPI-SCORE. The six variables that have been automatically selected by our machine learning algorithm were the WHO severity classification, acute kidney injury, age, Lactate Dehydrogenase Levels (LDH), lymphocytes and activated prothrombin time (aPTT). Receiver Operation Characteristic (ROC) curve indexes hereby obtained were 83.8% and 91% for the models based on WHO classification only and our EPI-SCORE, respectively. Conclusions: Our study shows that the WHO severity classification is reliable in predicting a severe outcome among COVID-19 patients. The addition to this classification of a few clinical and laboratory variables as per our COVID-19 EPI-SCORE has demonstrated to significantly increase its accuracy.
A Predicted Mannoprotein Cmp1 Regulates Fungal Virulence in Cryptococcus neoformans
Authors: Han Lian-Tao , Wu Lei , Liu Tong-Bao
Published: October 2020

The capsule of the fungal pathogen Cryptococcus neoformans consists of glucuronoxylomannan (GXM), glucuronoxylomannogalactan (GXMGal), and mannoproteins (MPs). MPs are a kind of glycoproteins with low content but high immunogenicity, which can stimulate the immune protection of the host. However, there is not much information about the role of mannoproteins in virulence of the human fungal pathogen C. neoformans. In this study, we reported the identification and functional analysis of a predicted mannoprotein Cmp1 that regulates fungal virulence in C. neoformans. Gene expression pattern analysis indicates that the CMP1 gene was ubiquitously expressed at all stages of cryptococcal development. Subcellular localization analysis indicated that Cmp1 was localized in the cytoplasm of cryptococcal cells. Disruption or overexpression of CMP1 results in impairing capsule formation in Cryptococcus, but it does not affect the melanin production and sensitivity under various stress conditions, nor does it affect the sexual reproduction process of Cryptococcus. Survival assay showed that the pathogenicity of the cmp1Δ mutant or the CMP1 overexpression strain was significantly attenuated in a murine inhalation model of cryptococcosis. In conclusion, our findings implied that the mannoprotein Cmp1 is required for the virulence of C. neoformans.
The Impact of Mastitis on the Biochemical Parameters, Oxidative and Nitrosative Stress Markers in Goat’s Milk: A Review
Authors: Novac Cristiana S. , Andrei Sanda
Published: October 2020

Goat mastitis has become one of the most frequently diagnosed conditions in goat farms, with significant economic impact on the dairy industry. Inflammation of the mammary gland poses serious consequences on milk composition, with changes regarding biochemical parameters and oxidative stress markers. The aim of this paper is to present the most recent knowledge on the main biochemical changes that occur in the mastitic milk, as well as the overall effect of the oxidative and nitrosative stress on milk components, focusing on both enzymatic and nonenzymatic antioxidant markers. Mastitis in goats is responsible for a decrease in milk production, change in protein content with pronounced casein hydrolysis, and reduction in lactose concentration and milk fat. Milk enzymatic activity also undergoes changes, regarding indigenous enzymes and those involved in milk synthesis. Furthermore, during mastitis, both the electrical conductivity and the milk somatic cell count are increased. Intramammary infections are associated with a reduced milk antioxidant capacity and changes in catalase, lactoperoxidase, glutathione peroxidase or superoxide dismutase activity, as well as reduced antioxidant vitamin content. Mastitis is also correlated with an increase in the concentration of nitric oxide, nitrite, nitrate and other oxidation compounds, leading to the occurrence of nitrosative stress.
Taxonomy and Phylogenetic Research on Ralstonia solanacearum Species Complex: A Complex Pathogen with Extraordinary Economic Consequences
Authors: Paudel Sujan , Dobhal Shefali , Alvarez Anne M. , Arif Mohammad
Published: October 2020

The bacterial wilt pathogen, first known as Bacillus solanacearum, has undergone numerous taxonomic changes since its first description in 1896. The history and significance of this pathogen is covered in this review with an emphasis on the advances in technology that were used to support each reclassification that finally led to the current separation of Ralstonia solanacearum into three genomic species. Frequent name changes occurred as methodology transitioned from phenotypic, biochemical, and molecular studies, to genomics and functional genomics. The diversity, wide host range, and geographical distribution of the bacterial wilt pathogen resulted in its division into three species as genomic analyses elucidated phylogenetic relationships among strains. Current advances in phylogenetics and functional genomics now open new avenues for research into epidemiology and control of the devastating bacterial wilt disease.
A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI
Authors: Bojarska Joanna , Remko Milan , Breza Martin , Madura Izabela , Fruziński Andrzej , Wolf Wojciech M.
Published: October 2020

Proline is a unique, endogenous amino acid, prevalent in proteins and essential for living organisms. It is appreciated as a tecton for the rational design of new bio-active substances. Herein, we present a short overview of the subject. We analyzed 2366 proline-derived structures deposited in the Cambridge Structure Database, with emphasis on the angiotensin-converting enzyme inhibitors. The latter are the first-line antihypertensive and cardiological drugs. Their side effects prompt a search for improved pharmaceuticals. Characterization of tectons (molecular building blocks) and the resulting supramolecular synthons (patterns of intermolecular interactions) involving proline derivatives, as presented in this study, may be useful for in silico molecular docking and macromolecular modeling studies. The DFT, Hirshfeld surface and energy framework methods gave considerable insight into the nature of close inter-contacts and supramolecular topology. Substituents of proline entity are important for the formation and cooperation of synthons. Tectonic subunits contain proline moieties characterized by diverse ionization states: -N and -COOH(-COO−), -N+ and -COOH(-COO−), -NH and -COOH(-COO−), -NH+ and -COOH(-COO−), and -NH2+ and -COOH(-COO−). Furthermore, pharmacological profiles of ACE inhibitors and their impurities were determined via an in silico approach. The above data were used to develop comprehensive classification, which may be useful in further drug design studies.
Anakinra Reduces Epileptogenesis, Provides Neuroprotection, and Attenuates Behavioral Impairments in Rats in the Lithium–Pilocarpine Model of Epilepsy
Authors: Dyomina Alexandra V. , Zubareva Olga E. , Smolensky Ilya V. , Vasilev Dmitry S. , Zakharova Maria V. , Kovalenko Anna A. , Schwarz Alexander P. , Ischenko Alexander M. , Zaitsev Aleksey V.
Published: October 2020

Temporal lobe epilepsy is a widespread chronic disorder that manifests as spontaneous seizures and is often characterized by refractoriness to drug treatment. Temporal lobe epilepsy can be caused by a primary brain injury; therefore, the prevention of epileptogenesis after a primary event is considered one of the best treatment options. However, a preventive treatment for epilepsy still does not exist. Neuroinflammation is directly involved in epileptogenesis and neurodegeneration, leading to the epileptic condition and cognitive decline. In the present study, we aimed to clarify the effect of treatment with a recombinant form of the Interleukin-1 receptor antagonist (anakinra) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that anakinra administration during the latent phase of the model significantly suppressed the duration and frequency of spontaneous recurrent seizures in the chronic phase. Moreover, anakinra administration prevented some behavioral impairments, including motor hyperactivity and disturbances in social interactions, during both the latent and chronic periods. Histological analysis revealed that anakinra administration decreased neuronal loss in the CA1 and CA3 areas of the hippocampus but did not prevent astro- and microgliosis. The treatment increased the expression level of the solute carrier family 1 member 2 gene (Slc1a2, encoding excitatory amino acid transporter 2 (EAAT2)) in the hippocampus, potentially leading to a neuroprotective effect. However, the increased gene expression of proinflammatory cytokine genes (Interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa)) and astroglial marker genes (glial fibrillary acidic protein (Gfap) and inositol 1,4,5-trisphosphate receptor type 2 (Itpr2)) in experimental rats was not affected by anakinra treatment. Thus, our data demonstrate that the administration of anakinra during epileptogenesis has some beneficial disease-modifying effects.
Precision Medicine in Neurology: The Inspirational Paradigm of Complement Therapeutics
Authors: Gavriilaki Maria , Kimiskidis Vasilios K. , Gavriilaki Eleni
Published: October 2020

Precision medicine has emerged as a central element of healthcare science. Complement, a component of innate immunity known for centuries, has been implicated in the pathophysiology of numerous incurable neurological diseases, emerging as a potential therapeutic target and predictive biomarker. In parallel, the innovative application of the first complement inhibitor in clinical practice as an approved treatment of myasthenia gravis (MG) and neuromyelitis optica spectrum disorders (NMOSD) related with specific antibodies raised hope for the implementation of personalized therapies in detrimental neurological diseases. A thorough literature search was conducted through May 2020 at MEDLINE, EMBASE, Cochrane Library and ClinicalTrials.gov databases based on medical terms (MeSH)” complement system proteins” and “neurologic disease”. Complement’s role in pathophysiology, monitoring of disease activity and therapy has been investigated in MG, multiple sclerosis, NMOSD, spinal muscular atrophy, amyotrophic lateral sclerosis, Parkinson, Alzheimer, Huntington disease, Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, stroke, and epilepsy. Given the complexity of complement diagnostics and therapeutics, this state-of-the-art review aims to provide a brief description of the complement system for the neurologist, an overview of novel complement inhibitors and updates of complement studies in a wide range of neurological disorders.
Efficacy of Local Minocycline Agents in Treating Peri-Implantitis: An Experimental In Vivo Study in Beagle Dogs
Authors: Yoon Sung-Wook , Kim Myong-Ji , Paeng Kyeong-Won , Yu Kyeong Ae , Lee Chong-Kil , Song Young Woo , Cha Jae-Kook , Jung Ui-Won
Published: October 2020

Background: Local delivery agents (LDA) have the advantage of delivering the antibiotics at high concentrations to the targeted sites. However, the constant flow of gingival crevicular fluids and saliva may restrict their efficacy. Therefore, the drug sustainability and pharmacodynamic properties of any proposed LDA should be evaluated. Methods: Four dental implants were placed unilaterally in the edentulous mandible of six beagle dogs. Peri-implantitis were experimentally induced using silk-ligatures. Each implant was randomly allocated to receive one of the following four treatments: (i) MC (Chitosan-alginate (CA) minocycline), (ii) MP (CA-without minocycline), (iii) PG (Polyacrylate-glycerin minocycline), and (iv) Control (mechanical debridement only). Mechanical therapies and LDAs were administered into the gingival sulcus two times at a 4-week interval. Drug sustainability as well as clinical, radiographical, and immunohistochemical (IHC) analyses were conducted to evaluate the efficacies of treatments. Results: Reduced mean probing depth was observed in all of the test groups after the second delivery. A minimal marginal bone level change was observed during the treatment period (MP (−0.06 ± 0.53 mm) to PG (−0.25 ± 0.42 mm)). The distribution of IHC cell marker analysis of all targeted antibodies ranged from 6.34% to 11.33%. All treatment outcomes between the test groups were comparable. A prolonged retention of LDA was observed from CA microspheres (MC and MP) at both administrations (p < 0.017) and prolonged sustainability of bacteriostatic effect was observed from MC compared to PG after the second administration (p < 0.05). Conclusions: Prolonged retention of CA microspheres was observed and the longer bacteriostatic effect was observed from the MC group. Mechanical debridement with adjunct LDA therapy may impede peri-implantitis progression, however, prolonged drug action did not lead to improved treatment outcome.
Vacuum Compression Molding as a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations
Authors: Shadambikar Gauri , Kipping Thomas , Di-Gallo Nicole , Elia Alessandro-Giuseppe , Knüttel Anja-Nadine , Treffer Daniel , Repka Michael. A
Published: October 2020

Hot-melt extrusion (HME) is the most preferred and effective method for manufacturing amorphous solid dispersions at production scale, but it consumes large amounts of samples when used for formulation development. Herein, we show a novel approach to screen the polymers by overcoming the disadvantage of conventional HME screening by using a minimum quantity of active pharmaceutical ingredient (API). Vacuum Compression Molding (VCM) is a fusion-based method to form solid specimens starting from powders. This study aimed to investigate the processability of VCM for the creation of amorphous formulations and to compare its results with HME-processed formulations. Mixtures of indomethacin (IND) with drug carriers (Parteck® MXP, Soluplus®, Kollidon® VA 64, Eudragit® EPO) were processed using VCM and extrusion technology. Thermal characterization was performed using differential scanning calorimetry, and the solid-state was analyzed via X-ray powder diffraction. Dissolution studies in the simulated gastric fluid were performed to evaluate the drug release. Both technologies showed similar results proving the effectiveness of VCM as a screening tool for HME-based formulations.
Detailed Genetic Analysis for Identifying QTLs Associated with Drought Tolerance at Seed Germination and Seedling Stages in Barley
Authors: Moursi Yasser S. , Thabet Samar G. , Amro Ahmed , Dawood Mona F. A. , Baenziger P. Stephen , Sallam Ahmed
Published: October 2020

Drought induces several challenges for plant development, growth, and production. These challenges become more severe, in particular, in arid and semiarid countries like Egypt. In terms of production, barley ranks fourth after wheat, maize, and rice. Seed germination and seedling stages are critical stages for plant establishment and growth. In the current study, 60 diverse barley genotypes were tested for drought tolerance using two different treatments: control (0-PEG) and drought (20%-PEG). Twenty-two traits were estimated for seed germination and seedling parameters. All traits were reduced under drought stress, and a significant variation was found among genotypes under control and stress conditions. The broad-sense heritability estimates were very high under both control and drought for all traits. It ranged from 0.63 to 0.97 under the control condition and from 0.89 to 0.97 under drought, respectively. These high heritabilities suggested that genetic improvement of drought tolerance in barley at both stages is feasible. The principal component analysis revealed that root-related parameters account for the largest portion of phenotypic variation in this collection. The single-marker analysis (SMA) resulted in 71 quantitative trait loci (QTLs) distributed across the seven chromosomes of barley. Thirty-three QTLs were detected for root-length-related traits. Many hotspots of QTLs were detected for various traits. Interestingly, some markers controlled many traits in a pleiotropic manner; thus, they can be used to control multiple traits at a time. Some QTLs were constitutive, i.e., they are mapped under control and drought, and targeting these QTLs makes the selection for drought tolerance a single-step process. The results of gene annotation analysis revealed very potential candidate genes that can be targeted to select for drought tolerance.
Early Season Symptoms on Stem, Inflorescences and Flowers of Grapevine Associated with Botryosphaeriaceae Species
Authors: Reis Pedro , Gaspar Ana , Alves Artur , Fontaine Florence , Lourenço Inês , Saramago José , Mota Mariana , Rego Cecília
Published: October 2020

Botryosphaeria dieback caused by several Botryosphaeriaceae species is one of the most important grapevine trunk diseases affecting vineyards worldwide. These fungi cause wedge-shaped perennial cankers and black streaking of the wood and have also been associated with intervein leaf chlorosis, dried or mummified berries, and eventually, the death of the plant. Early season symptoms may sometimes be disregarded by growers, being mistaken with symptoms from other diseases such as downy mildew or botrytis rot. Currently, few studies are available to determine what species may be causing these early season symptoms in grapevines. During the 2018 season, during the flowering period, grapevine samples showing necrosis on green shoots, dried inflorescences, and flowers, were collected in vineyards throughout the central regions of Portugal. Isolations were performed from symptomatic organs, and twenty-three isolates of Botryosphaeriaceae were selected. An analysis of the ITS and part of the translation elongation factor 1-α sequences was performed, revealing that the two main species apparently responsible for these symptoms were Diplodia seriata and Neofusicoccum parvum. In pathogenicity tests conducted on 1-year-old plants grown under controlled conditions in a greenhouse and on field-grown clusters, symptoms were reproduced, confirming the pathogenic behavior of the selection of isolates.
Plant Histone HTB (H2B) Variants in Regulating Chromatin Structure and Function
Authors: Khadka Janardan , Pesok Anat , Grafi Gideon
Published: October 2020

Besides chemical modification of histone proteins, chromatin dynamics can be modulated by histone variants. Most organisms possess multiple genes encoding for core histone proteins, which are highly similar in amino acid sequence. The Arabidopsis thaliana genome contains 11 genes encoding for histone H2B (HTBs), 13 for H2A (HTAs), 15 for H3 (HTRs), and 8 genes encoding for histone H4 (HFOs). The finding that histone variants may be expressed in specific tissues and/or during specific developmental stages, often displaying specific nuclear localization and involvement in specific nuclear processes suggests that histone variants have evolved to carry out specific functions in regulating chromatin structure and function and might be important for better understanding of growth and development and particularly the response to stress. In this review, we will elaborate on a group of core histone proteins in Arabidopsis, namely histone H2B, summarize existing data, and illuminate the potential function of H2B variants in regulating chromatin structure and function in Arabidopsis thaliana.
Selection of Reference Genes for qRT-PCR Analysis in Medicinal Plant Glycyrrhiza under Abiotic Stresses and Hormonal Treatments
Authors: Li Yuping , Liang Xiaoju , Zhou Xuguo , Wu Zhigeng , Yuan Ling , Wang Ying , Li Yongqing
Published: October 2020

Best known as licorice, Glycyrrhiza Linn., a genus of herbaceous perennial legume, has been used as a traditional herbal medicine in Asia and a flavoring agent for tobacco and food industry in Europe and America. Abiotic stresses and hormonal treatments can significantly impact the development and metabolism of secondary metabolites in Glycyrrhiza. To better understand the biosynthesis of the trace-amount bioactive compounds, we first screened for the suitable reference genes for quantitative real-time reverse transcription PCR (qRT-PCR) analysis in Glycyrrhiza. The expression profiles of 14 candidate reference genes, including Actin1 (ACT), Clathrin complex AP1 (CAC), Cyclophilin (CYP), Heat-shock protein 40 (DNAJ), Dehydration responsive element binding gene (DREB), Translation elongation factor1 (EF1), Ras related protein (RAN), Translation initiation factor (TIF1), β-Tubulin (TUB), Ubiquitin-conjugating enzyme E2 (UBC2), ATP binding-box transpoter 2 (ABCC2), COP9 signal compex subunit 3 (COPS3), Citrate synthase (CS), and R3H domain protein 2 (R3HDM2) from two congeneric species, Glycyrrhiza uralensis F. and Glycyrrhiza inflata B., were examined under abiotic stresses (osmotic and salinity) and hormonal treatments (Abscisic acid (ABA) and methyl jasmonic acid (MeJA)) using a panel of software, including geNorm, NormFinder, BestKeeper, and Delta CT. The overall stability, however, was provided by RefFinder, a comprehensive ranking system integrating inputs from all four algorithms. In G. uralensis, the most stable reference genes under osmotic stress, salt stress, ABA treatment, and MeJA treatment were TIF1, DNAJ, CS, and ABCC2 for leaves and DNAJ, DREB, CAC, and CAC for roots, respectively. In comparison, the top ranked genes were TUB, CAC, UBC2, and RAN for leaves and TIF1, ABCC2, CAC, and UBC2 for roots, respectively, under stress and hormonal treatments in G. inflata. ACT and TIF1, on the other hand, were the least stable genes under the most experimental conditions in the two congeneric species. Finally, our survey of the reference genes in legume shows that EF, ACT, UBC2, and TUB were the top choices for the abiotic stresses while EF, UBC2, CAC, and ABCC2 were recommended for the hormonal treatments in Leguminosae. Our combined results provide reliable normalizers for accurate gene quantifications in Glycyrrhiza species, which will allow us to exploit its medicinal potential in general and antiviral activities in particular.