bluuebunny/crossref_metadata_2025 huggingface dataset:
Public Health Implications of Wasting and Stunting Relationship in Children under Five Years Highly Vulnerable to Undernutrition in Guatemala: The REDAC Study
Authors: López-Ejeda Noemí , Medialdea Laura , Vargas Antonio , Coronado Jessica , García-Arias Miguel Ángel , Marrodán María Dolores
Published: September 2022

(1) Background: Guatemala is the Latin American country with the highest prevalence of childhood stunting. Short height can bias the diagnosis of wasting when using the weight-for-height indicator. The aim of this study was to evaluate the diagnostic concordance of the anthropometric indicators of wasting and the relationship between wasting and stunting in children from highly vulnerable communities in Guatemala. (2) Methods: The sample consisted of 13,031 anthropometric records of children under five years of age (49.5% girls, average age of 27.9 months), including weight, height, and mid-upper arm circumference (MUAC), collected in March–August 2019. The proportions of stunting, underweight, and wasting, assessed by three different indicators, as well as their concurrence through the Composite Index of Anthropometric Failure were calculated. (3) Results: Stunting affected 73% of the sample, and 74.2% showed anthropometric failure. Wasting varied by indicator (weight-for-height: 2.8%; MUAC: 4.4%; MUAC-for-age: 10.6%). Concordance between MUAC and weight-for-height was very low (Kappa: 0.310; sensitivity: 40.9%). MUAC identified more wasted children in the stunted group (53.6% vs. 26.5%), while the opposite occurred in the non-stunted group (34.8% vs. 46.7%). (4) Conclusion: The presence of stunting affected the diagnosis of wasting, and both indicators should be included as diagnostic criteria for screening campaigns and in the treatment of moderate to acute wasting in vulnerable populations affected by multiple forms of undernutrition.
Geographic Variations in Dietary Patterns and Their Associations with Overweight/Obesity and Hypertension in China: Findings from China Nutrition and Health Surveillance (2015–2017)
Authors: Zhao Rongping , Zhao Liyun , Gao Xiang , Yang Fan , Yang Yuxiang , Fang Hongyun , Ju Lahong , Xu Xiaoli , Guo Qiya , Li Shujuan , Cheng Xue , Cai Shuya , Yu Dongmei , Ding Gangqiang
Published: September 2022

Regional dietetic cultures were indicated in China, but how dietary patterns geographically varied across China is unknown. Few studies systematically investigated the association of dietary patterns with overweight/obesity and hypertension and the potential mechanism with a national sample. This study included 34,040 adults aged 45 years and older from China Nutrition and Health Surveillance (2015–2017), who had complete outcome data, reliable intakes of calorie and cooking oils, unchanged diet habits, and without diagnosed cancer or cardiovascular disease. Outcomes were overweight/obesity and hypertension. By using the Gaussian finite mixture models, four dietary patterns were identified—common rice-based dietary pattern (CRB), prudent diversified dietary pattern (PD), northern wheat-based dietary pattern (NWB), and southern rice-based dietary pattern (SRB). Geographic variations in dietary patterns were depicted by age–sex standardized proportions of each pattern across 31 provinces in China. We assessed the association of these dietary patterns with outcomes and calculated the proportion mediated (PM) by overweight/obesity in the association of the dietary patterns with hypertension. Evident geographic disparities in dietary patterns across 31 provinces were observed. With CRB as reference group and covariates adjusted, the NWB had higher odds of being overweight/obese (odds ratio (OR) = 1.44, 95% confidence interval (CI): 1.36–1.52, p < 0.001) and hypertension (OR = 1.07, 95%CI: 1.01–1.14, p < 0.001, PM = 43.2%), while the SRB and the PD had lower odds of being overweight/obese (ORs = 0.84 and 0.92, 95%CIs: 0.79–0.89 and 0.85–0.99, p < 0.001 for both) and hypertension (ORs = 0.93 and 0.87, 95%CIs: 0.87–0.98 and 0.80–0.94, p = 0.038 for SRB and p < 0.001 for PD, PMs = 27.8% and 9.9%). The highest risk of overweight/obesity in the NWB presented in relatively higher carbohydrate intake (about 60% of energy) and relatively low fat intake (about 20% of energy). The different trends in the association of protein intake with overweight/obesity among dietary patterns were related to differences in animal food sources. In conclusion, the geographic distribution disparities of dietary patterns illustrate the existence of external environment factors and underscore the need for geographic-targeted dietary actions. Optimization of the overall dietary pattern is the key to the management of overweight/obesity and hypertension in China, with the emphasis on reducing low-quality carbohydrate intake, particularly for people with the typical northern diet, and selection of animal foods, particularly for people with the typical southern diet.
The Barrier-Enhancing Function of Soluble Yam (Dioscorea opposita Thunb.) Polysaccharides in Rat Intestinal Epithelial Cells as Affected by the Covalent Se Conjugation
Authors: Wang Zhen-Xing , Zhao Xin-Huai
Published: September 2022

The non-starch yam polysaccharides (YP) are the bioactive substances of edible yam, while Se is an essential nutrient for the human body. Whether a covalent conjugation of Se to YP might cause bioactivity change for the resultant selenylated YP in the intestine is still insufficiently studied, including the critical intestinal barrier function. In this study, two selenylated YP products, namely, YPSe-I and YPSe-II, with corresponding Se contents of 795 and 1480 mg/kg, were obtained by the reaction of YP and Na2SeO3 in the presence of HNO3 and then assessed for their bioactivities to a cell model (i.e., rat intestinal epithelial IEC-6 cells). The results showed that YP, YPSe-I, and YPSe-II at 5–80 μg/mL dosages could promote cell growth with treatment times of 12–24 h. The three samples also could improve barrier integrity via increasing cell monolayer resistance and anti-bacterial activity against E. coli or by reducing paracellular permeability and bacterial translocation. Additionally, the three samples enhanced F-actin distribution and promoted the expression of the three tight junction proteins, namely, zonula occluden-1, occludin, and claudin-1. Meanwhile, the expression levels of ROCK and RhoA, two critical proteins in the ROCK/RhoA singling pathway, were down-regulated by these samples. Collectively, YPSe-I and, especially, YPSe-II were more potent than YP in enhancing the assessed bioactivities. It is thus concluded that this chemical selenylation of YP brought about enhanced activity in the cells to promote barrier integrity, while a higher selenylation extent of the selenylated YP induced much activity enhancement. Collectively, the results highlighted the important role of the non-metal nutrient Se in the modified polysaccharides.
Food Hubs as a Means to Promote Food Security in Post-Secondary Institutions: A Scoping Review
Authors: Murphy Rachel A. , Guo Yu Jacqueline , Cordeiro Heloise Sierra Melo Pinto , Stroshein Sumara , Hamilton Casey , Kozicky Sara
Published: September 2022

An estimated 20 to 50% of post-secondary students experience food insecurity. Students who are food insecure are more likely to have poor health and lower academic performance relative to food secure peers. Food hubs are physical or digital spaces that provide access to food initiatives and wraparound programs such as employment placement or income support are increasingly of interest as a means to respond to food insecurity. We conducted a scoping review to identify best practices and effective approaches to food hubs that promote food security in post-secondary institutions in North America. The Medline, Embase, CAB Direct and Web of Science databases were searched. A total of 4637 articles were identified and screened by two reviewers. Four articles were included. They encompassed a mix of interventions: a campus pantry and garden, a food rescue program, food literacy-based curriculum and a toolkit to support implementation of interventions on campus. The heterogeneity of studies precluded identification of best practices, but positive impacts of all interventions were noted on metrics such as self-efficacy and greater awareness of food insecurity. The gap in evidence on effective approaches that promote campus food security is a critical barrier to development and implementation of interventions, and should be addressed in future studies.
SMOFlipid Impact on Growth and Neonatal Morbidities in Very Preterm Infants
Authors: Asfour Suzan S. , Alshaikh Belal , AlMahmoud Latifah , Sumaily Haider H. , Alodhaidan Nabeel A. , Alkhourmi Mousa , Abahussain Hissah A. , Khalil Thanaa M. , Albeshri Bushra A. , Alhamidi Aroub A. , Al-Anazi Maha R. , Asfour Raneem S. , Al-Mouqdad Mountasser M.
Published: September 2022

The soybean oil, medium-chain triglycerides, olive oil, and fish oil lipid (SMOFlipid) is increasingly being used worldwide without definite evidence of its benefits. We examined the effect of SMOFlipid on growth velocity and neonatal morbidities in very preterm infants. Very preterm infants who received soybean-based lipid emulsion between January 2015 and 2018 were compared with those who received SMOFlipids between 2019 and January 2022 in our neonatal tertiary center. Linear regression analysis was conducted to analyze the association between type of lipid emulsion and growth velocity. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber–White) were applied to adjust for potential confounding factors. A total of 858 infants met our inclusion criteria. Of them, 238 (27.7%) received SMOFlipid. SMOFlipid was associated with lower growth velocity between birth and 36-week corrected gestational age compared with intralipid Δ weight z-score (adjusted mean difference (aMD) −0.67; 95% CI −0.69, −0.39). Subgroup analysis indicated that mainly male infants in the SMOFlipid–LE group had a lower Δ weight z-score compared to those in the intralipid group (p < 0.001), with no difference observed in females (p = 0.82). SMOFlipid was associated with a lower rate of bronchopulmonary dysplasia (BPD) (aRR 0.61; 95% CI 0.46, 0.8) and higher rate of late-onset sepsis compared with intralipid (aRR 1.44; 95% CI 1.22–1.69). SMOFlipid was associated with lower growth velocity and BPD but higher rate of late-onset sepsis—it is a double-edged sword.
Dietary Behaviors among New Users of Meal-Kit Services during the Early Months of the COVID-19 Pandemic
Authors: Robinson-Oghogho Joelle N. , Thorpe Roland J. , Neff Roni A.
Published: September 2022

The COVID-19 pandemic changed the way people acquired food, including increased use of meal-kit delivery services. Investigators analyzed data from a national survey of US adults collected between July 2020 and September 2020, to describe new users of meal-kit services during the pandemic and explore associations between new use of meal-kits and dietary behaviors. Bivariate and multivariate regression analyses were conducted to identify differences in demographic characteristics and reported dietary behaviors between new and never meal-kit users. Nearly all new meal-kit users were under the age of 55 years (92.5%), lived in urban areas (90.1%), and reported having children in their households (82%). A higher proportion of new users were current SNAP participants (32.8%) compared to never users (17.1%). Compared to never users, new users of meal-kit services reported eating more fruits and vegetables (PR: 1.95, 95% CI: 1.42, 2.68), and more red and processed meats (PR: 2.39, 95% CI: 1.49–3.85) since the pandemic began. Results suggest that meal-kit services may have been a useful resource for certain populations during the early months of COVID-19 and are potentially associated with increased consumption of certain foods. Further research examining the continued use and the influence of meal-kit services on diet is needed.
The Link between Food Environment and Colorectal Cancer: A Systematic Review
Authors: Masdor Noor Azreen , Mohammed Nawi Azmawati , Hod Rozita , Wong Zhiqin , Makpol Suzana , Chin Siok-Fong
Published: September 2022

Food and diet are critical risk factors for colorectal cancer (CRC). Food environments (FEs) can contribute to disease risk, including CRC. This review investigated the link between FEs and CRC incidence and mortality risk. The systematic search of studies utilised three primary journal databases: PubMed, Scopus, and Web of Science. Retrieved citations were screened and the data were extracted from articles related to the FE-exposed populations who were at risk for CRC and death. We evaluated ecological studies and cohort studies with quality assessment and the Newcastle-Ottawa Quality Assessment Form for Cohort Studies, respectively. A descriptive synthesis of the included studies was performed. Out of 89 articles identified, eight were eligible for the final review. The included studies comprised six ecological studies and two cohort studies published from 2013 to 2021. Six articles were from the US, one was from Africa, and one was from Switzerland. All eight studies were of good quality. The significant finding was that CRC incidence was associated with the availability of specific foods such as red meat, meat, animal fats, energy from animal sources, and an unhealthy FE. Increased CRC mortality was linked with the availability of animal fat, red meat, alcoholic beverages, and calorie food availability, residence in food deserts, and lower FE index. There were a variety of associations between CRC and the FE. The availability of specific foods, unhealthy FE, and food desserts impact CRC incidence and mortality. Creating a healthy FE in the future will require focus and thorough planning.
Realgar Alleviated Neuroinflammation Induced by High Protein and High Calorie Diet in Rats via the Microbiota-Gut-Brain Axis
Authors: Feng Cong , Li Aihong , Yin Chenhui , Wang Siying , Jin Weiyuan , Liu Yi , Huo Taoguang , Jiang Hong
Published: September 2022

Purpose: Gastrointestinal heat retention syndrome (GHRS) often occurs in adolescents, resulting into nervous system injury. Realgar, an arsenic mineral with neuroprotective effect, has been widely used to treat GHRS. However, its mechanism of action remains unknown. Methods: A GHRS rat model was established using a high protein and high calorie diet. We performed macroscopic characterization by assessing bowel sounds, hot/cold preference, anal temperature, and fecal features. Atomic fluorescence spectroscopy was employed to evaluate brain arsenic level while hippocampal ultrastructural changes were analyzed using transmission electron microscopy. In addition, inflammatory cytokines and BBB breakdown were analyzed by western blotting, immunofluorescence assays, and immunohistochemistry staining. We also evaluated hippocampal metabolites by LC-MS while fecal microorganisms were assessed by 16S rDNA sequencing. Results: Our data showed that the high protein and high calorie diet induced GHRS. The rat model depicted decreased bowel sounds, increased fecal characteristics score, preference for low temperature zone, and increased anal temperature. In addition, there was increase in inflammatory factors IL-6, Iba-1, and NF-κB p65 as well as reduced BBB structural protein Claudin-5 and Occludin. The data also showed appearance of hippocampus metabolites disorder and fecal microbial imbalance. Realgar treatment conferred a neuroprotective effect by inhibiting GHRS-specific characteristics, neuroinflammatory response, BBB impairment, metabolites disorder, and microbial imbalance in the GHRS rat model. Conclusion: Taken together, our analysis demonstrated that realgar confers a neuroprotective effect in GHRS rats through modulation of the microbiota-gut-brain axis.
The Intake of Antioxidant Capacity of Children Depends on Their Health Status
Authors: Navajas-Porras Beatriz , Pérez-Burillo Sergio , Hinojosa-Nogueira Daniel , Douros Konstantinos , Pastoriza Silvia , Rufián-Henares José Ángel
Published: September 2022

The gastrointestinal digestion of food and further gut microbial activity render a myriad of different molecules that could be responsible for the biological activities that are classically assigned to their parent compounds. This has been previously shown for some phytochemicals whose antioxidant capacity was either increased or decreased after being metabolized by gut microbes. Whether a global antioxidant capacity that is extracted from food is determined by the gut microbial community structure is still not well described. In the present study, we in vitro digested and fermented 48 different foods that were submitted to different culinary treatments using the stools of lean children, obese children, celiac children and children with an allergy to cow’s milk proteins. Their antioxidant capacities were assessed with the DPPH and FRAP assays, and the percentage that each food contributed to their daily antioxidant intake as well as their antioxidant capacity by portion size was inferred. Overall, cereals, fruits and vegetables displayed a higher contribution to their daily antioxidant intake, while tubers, fish and meat exhibited a higher antioxidant capacity by serving size. The food that was fermented in the lean children’s and those children that were allergic to cow’s milk protein’s fecal material, showed a higher antioxidant capacity, which could imply that there is a larger role of the gut microbiota in this area.
Impact of Preoperative Visceral Fat Area Measured by Bioelectrical Impedance Analysis on Clinical and Oncologic Outcomes of Colorectal Cancer
Authors: Kim Kyeong Eui , Bae Sung Uk , Jeong Woon Kyung , Baek Seong Kyu
Published: September 2022

Background: Some studies have shown that an increase in visceral fat is associated with postoperative clinical and oncologic outcomes. However, no studies have used bioelectrical impedance analysis (BIA) to determine the effects of visceral fat on the oncologic outcomes of colorectal cancer (CRC). This study aimed to investigate the impact of preoperative visceral fat area measured by bioelectrical impedance analysis on clinical and oncologic outcomes of colorectal cancer Methods: This study included 203 patients who underwent anthropometric measurements by BIA before surgical treatment for CRC between January 2016 and June 2020. Results: According to the cut-off level of VFA by receiver operating characteristic curve analysis, 85 (40.5%) patients had a low VFA, and 119 (59.5%) had a high VFA. Multivariate analysis found that preoperative CRP (hazard ratio (HR), 3.882; 95% confidence interval (CI), 1.001–15.051; p = 0.050) and nodal stage (HR, 7.996; 95% CI, 1.414–45.209; p = 0.019) were independent prognostic factors for overall survival, while sex (HR, 0.110; 95% CI, 0.013–0.905; p = 0.040), lymphovascular invasion (HR, 3.560; 95% CI, 1.098–11.544; p = 0.034), and VFA (HR, 4.263; 95% CI, 1.280–14.196; p = 0.040) were independent prognostic factors for disease-free survival (DFS). Conclusions: Preoperative VFA measured by BIA had no significant impact on postoperative clinical outcomes and was an independent prognostic factor for disease-free survival.
Cross-Sectional Association of Blood Selenium with Glycemic Biomarkers among U.S. Adults with Normoglycemia in the National Health and Nutrition Examination Survey 2013–2016
Authors: Yang Jingli , Chen En , Choi Cheukling , Chan Kayue , Yang Qinghua , Rana Juwel , Yang Bo , Huang Chuiguo , Yang Aimin , Lo Kenneth
Published: September 2022

Selenium (Se) remains to have an inconsistent relationship with glycemic biomarkers and the risk of developing type 2 diabetes (T2D). Few studies have investigated the relationship between blood Se and glycemic biomarkers among people with normoglycemia. We conducted a cross-sectional analysis using the U.S. National Health and Nutrition Examination Survey 2013–2016. Multivariable linear regression models were developed to examine the associations of blood Se with glycemic biomarkers, namely, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), insulin, and the oral glucose tolerance test (OGTT). Blood Se was treated as continuous (per log-10 increment) and categorical exposure (in quartiles) in separate regression models. We assessed the dose–response relationships by restricted cubic spline analysis. After excluding the participants with T2D or incomplete data, 2706 participants were analyzed. The highest quartile of blood Se was associated with increased FPG [adjusted β = 0.12, 95% Confidence Intervals (CI) = 0.04, 0.20], OGTT (adjusted β = 0.29, 95% CI = 0.02, 0.56), HbA1c (adjusted β = 0.04, 95% CI = 0.00, 0.07), and insulin (adjusted β = 2.50, 95% CI = 1.05, 3.95) compared with the lowest quartile. Positive associations were also observed between every log-10 increment of blood Se level and glycemic biomarkers, except for OGTT. A positive linear dose–response relationship existed between blood Se and FPG (Poverall = 0.003, Pnonlinear = 0.073) and insulin (Poverall = 0.004, Pnonlinear =0.060). BMI, age, and smoking status modified the associations of the highest quartile of Se (compared with the lowest quartile) with glycemic biomarkers. Overall, positive associations of blood Se with glycemic biomarkers were observed among U.S. adults with normoglycemia. These findings implied that people with normoglycemia need to be aware of the level of Se and other mineral intakes from diet and supplements. Further research is required to identify the mechanisms of excess Se in the progression of diabetes.
Nudging Finnish Adults into Replacing Red Meat with Plant-Based Protein via Presenting Foods as Dish of the Day and Altering the Dish Sequence
Authors: Nykänen Esa-Pekka , Hoppu Ulla , Löyttyniemi Eliisa , Sandell Mari
Published: September 2022

This study investigated whether Finnish working-aged omnivores (n = 163) could be nudged into replacing red meat with a fava-bean-based protein source via “Dish of the Day” (DoD) and main dish sequence alteration (SA) strategies in a controlled real-world Finnish self-service buffet restaurant with smart scales (Flavoria® Multidisciplinary Research Platform). A further aim was to study whether the effectiveness of the strategies differed by gender, age, and body mass index. The participants were assigned one of four experimental treatments: standard menu (T1), DoD (T2), standard menu + SA (T3), or DoD + SA (T4). The participants could choose any amount or combination of salad components and casseroles with minced meat or fava bean protein. Being subjected to a DoD menu and/or SA had no effect on main dish choice or the share of the meat-based dish in the meal weight. Men were more likely to choose a meat-based main dish and had a higher share of the meat dish in the meal weight compared to women, but no differences were observed between those aged 18–29, 30–44, or 45–65 years or those who were normal weight, overweight, or obese. Future studies should have a larger sample size and investigate food choice motives such as price or environmental awareness.
Twelve Months of Time-Restricted Feeding Improves Cognition and Alters Microbiome Composition Independent of Macronutrient Composition
Authors: Hernandez Abbi R. , Watson Cory , Federico Quinten P. , Fletcher Rachel , Brotgandel Armen , Buford Thomas W. , Carter Christy S. , Burke Sara N.
Published: September 2022

Declining health, gut dysbiosis, and cognitive impairments are hallmarks of advanced age. While caloric restriction is known to robustly extend the healthspan and alter gut microbiome composition, it is difficult maintain. Time-restricted feeding or changes in dietary macronutrient composition could be feasible alternatives for enhancing late life cognitive and physical health that are easier to comply with for extended periods of time. To investigate this possibility, 8-month-old rats were placed on time-restricted feeding with a ketogenic or micronutrient- and calorically matched control diet for 13 months. A third group of rats was permitted to eat standard chow ad libitum during this time. At 22 months, all rats were tested on a biconditional association task and fecal samples were collected for microbiome composition analysis. Regardless of dietary composition, time-restricted-fed rats had better cognitive performance than ad libitum-fed rats. This observation could not be accounted for by differences in motivation, procedural or sensorimotor impairments. Additionally, there were significant differences in gut microbiome diversity and composition between all diet conditions. Allobaculum abundance was associated with cognitive task performance, indicating a link between gut health and cognitive outcomes in aged subjects. Overall, time restricted feeding had the largest influence on cognitive performance in aged rats.
Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3β Pathway
Authors: Zhang Qi , Hu Sijing , He Yuqiong , Song Zile , Shen Yi , Zhao Zihui , Zhang Quanlong , Qin Luping , Zhang Qiaoyan
Published: September 2022

Monotropein (Mon) is a kind of iridoid glycoside plant secondary metabolite primarily present in some edible and medicinal plants. The aim of this study was to investigate the effect of Mon on lipopolysaccharide (LPS)-induced inflammatory bone loss in mice and osteoclasts (OCs) derived from bone marrow-derived macrophages (BMMs), and explore the mechanisms underlying the effect of Mon on LPS-induced osteoclastogenesis. It was found that Mon markedly attenuated deterioration of the bone micro-architecture, enhanced tissue mineral content (TMC) and bone volume/total volume (BV/TV), reduced structure model index (SMI) and trabecular separation/spacing (Tb.Sp) in the bone tissue and decreased the activities of tartrate resistant acid phosphatase-5b (TRACP-5b), receptor activator NF-κB (RANK), and receptor activator NF-κB ligand (RANKL) as well as the serum levels of interleukin 6 (IL-6) and interleukin 1β (IL-1β) in LPS-treated mice. In addition, Mon treatment reduced the number of TRAP positive OCs in the bone tissue of LPS-treated mice and also exerted a stronger inhibitory effect on formation, differentiation, and F-actin ring construction of OCs derived from BMMs. Mon significantly inhibited the expression of the nuclear factor of activated T-cells c1 (NFATc1) and the immediate early gene (C-Fos) and nuclear translocation of NFATc1 in LPS-treated OCs, thereby inhibiting the expression of matrix metalloproteinase-9 (MMP-9), cathepsin K (CtsK), and TRAP. Mon significantly inhibited the expression of TRAF6, phosphorylation of P65, and degradation of IKBα, thus inhibiting the activation of NF-κB pathway in LPS-induced inflammatory mice and OCs derived from BMMs, and also inhibited LPS-induced phosphorylation of protein kinase B (Akt) and Glycogen synthase kinase 3β (GSK-3β) in OCs derived from BMMs. In conclusion, these results suggested that Mon could effectively inhibit osteoclastogenesis both in vitro and in vivo and therefore may prove to be potential option for prevention and treatment of osteoclastic bone resorption-related diseases.
Effect of Important Food Sources of Fructose-Containing Sugars on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Controlled Feeding Trials
Authors: Qi XinYe , Chiavaroli Laura , Lee Danielle , Ayoub-Charette Sabrina , Khan Tauseef A. , Au-Yeung Fei , Ahmed Amna , Cheung Annette , Liu Qi , Blanco Mejia Sonia , Choo Vivian L. , de Souza Russell J. , Wolever Thomas M. S. , Leiter Lawrence A. , Kendall Cyril W. C. , Jenkins David J. A. , Sievenpiper John L.
Published: September 2022

Background: Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control. Methods: MEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence. Results: We identified 64 controlled trials (91 trial comparisons, n = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses. Conclusions: Food source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control. Clinicaltrials.gov: (NCT02716870).
Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism
Authors: Watkins Oliver C. , Cracknell-Hazra Victoria K. B. , Pillai Reshma Appukuttan , Selvam Preben , Yong Hannah E. J. , Sharma Neha , Patmanathan Sathya Narayanan , Cazenave-Gassiot Amaury , Bendt Anne K. , Godfrey Keith M. , Lewis Rohan M. , Wenk Markus R. , Chan Shiao-Yng
Published: September 2022

Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with 13C-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 µM). Newly synthesized 13C-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of 13C-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of 13C-AA-triacylglycerides (TGs) relative to total placental 13C-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four 13C-AA-phospholipids and eleven 13C-AA-TGs, whilst 17 mM glucose increased 13C-AA-PC-40:8 and 13C-AA-LPC. Glucose-induced alterations in all 13C-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 µM myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications.
Evaluation of Quantitative Platforms for Single Target Mass Spectrometry Imaging
Authors: Bowman Andrew P. , Sawicki James , Talaty Nari N. , Buck Wayne R. , Yang Junhai , Wagner David S.
Published: September 2022

(1) Imaging of pharmaceutical compounds in tissue is an increasingly important subsection of Mass Spectrometry Imaging (MSI). Identifying proper target engagement requires MS platforms with high sensitivity and spatial resolution. Three prominent categories of drugs are small molecule drugs, antibody-drug conjugate payloads, and protein degraders. (2) We tested six common MSI platforms for their limit of detection (LoD) on a representative compound for each category: a Matrix-Assisted Laser Desorption/Ionization (MALDI) Fourier Transform Ion Cyclotron, a MALDI-2 Time-of-Flight (ToF), a MALDI-2 Trapped Ion Mobility Spectrometry ToF, a Desorption Electrospray Ionization Orbitrap, and 2 Atmospheric Pressure-MALDI Triple Quadrupoles. Samples were homogenized tissue mimetic models of rat liver spiked with known concentrations of analytes. (3) We found that the AP-MALDI-QQQ platform outperformed all 4 competing platforms by a minimum of 2- to 52-fold increase in LoD for representative compounds from each category of pharmaceutical. (4) AP-MALDI-QQQ platforms are effective, cost-efficient mass spectrometers for the identification of targeted analytes of interest.
Quality by Design of Pranoprofen Loaded Nanostructured Lipid Carriers and Their Ex Vivo Evaluation in Different Mucosae and Ocular Tissues
Authors: Rincón María , Espinoza Lupe Carolina , Silva-Abreu Marcelle , Sosa Lilian , Pesantez-Narvaez Jessica , Abrego Guadalupe , Calpena Ana Cristina , Mallandrich Mireia
Published: September 2022

Transmucosal delivery is commonly used to prevent or treat local diseases. Pranoprofen is an anti-inflammatory drug prescribed in postoperative cataract surgery, intraocular lens implantation, chorioretinopathy, uveitis, age-related macular degeneration or cystoid macular edema. Pranoprofen can also be used for acute and chronic management of osteoarthritis and rheumatoid arthritis. Quality by Design (QbD) provides a systematic approach to drug development and maps the influence of the formulation components. The aim of this work was to develop and optimize a nanostructured lipid carrier by means of the QbD and factorial design suitable for the topical management of inflammatory processes on mucosal tissues. To this end, the nanoparticles loading pranoprofen were prepared by a high-pressure homogenization technique with Tween 80 as stabilizer and Lanette® 18 as the solid lipid. From, the factorial design results, the PF-NLCs-N6 formulation showed the most suitable characteristics, which was selected for further studies. The permeability capacity of pranoprofen loaded in the lipid-based nanoparticles was evaluated by ex vivo transmucosal permeation tests, including buccal, sublingual, nasal, vaginal, corneal and scleral mucosae. The results revealed high permeation and retention of pranoprofen in all the tissues tested. According to the predicted plasma concentration at the steady-state, no systemic effects would be expected, any neither were any signs of ocular irritancy observed from the optimized formulation when tested by the HET-CAM technique. Hence, the optimized formulation (PF-NLCs-N6) may offer a safe and attractive nanotechnological tool in topical treatment of local inflammation on mucosal diseases.
Combined In Silico and In Vitro Evidence Supporting an Aurora A Kinase Inhibitory Role of the Anti-Viral Drug Rilpivirine and an Anti-Proliferative Influence on Cancer Cells
Authors: Islam Saiful , Teo Theodosia , Kumarasiri Malika , Slater Martin , Martin Jennifer H. , Wang Shudong , Head Richard
Published: September 2022

The global burden of cancer necessitates rapid and ongoing development of effective cancer therapies. One promising approach in this context is the repurposing of existing non-cancer drugs for cancer indications. A key to this approach is selecting the cellular targets against which to identify novel repurposed drugs for pre-clinical analysis. Protein kinases are highly sought-after anticancer drug targets since dysregulation of kinases is the hallmark of cancer. To identify potential kinase-targeted drug candidates from the existing portfolio of non-cancer therapeutics, we used combined in silico and in vitro approaches, including ligand-based 3D screening followed by biochemical and cellular assessments. This strategy revealed that the anti-viral drug rilpivirine is an Aurora A kinase inhibitor. In view of previous findings implicating Aurora A kinase in abnormal cell cycle regulation, we also examined the influence of rilpivirine on the growth of T47D breast cancer cells. Herein, we detail the identification of rilpivirine as an Aurora A kinase inhibitor, its molecular basis of inhibitory activity towards this kinase, and its Aurora A-mediated anticancer mechanisms in T47D cells. Our results illustrate the value of integrated in silico and in vitro screening strategies in identifying repurposed drug candidates and provide a scientific basis for further exploring the potential anticancer properties of the anti-viral drug rilpivirine.
Manufacturability of a Tetraethyl Orthosilicate-Based Hydrogel for Use as a Single Application Otitis Externa Therapeutic
Authors: Barrett-Catton Emma , Arrigali Elizabeth M. , Serban Bogdan A. , Sandau Kolton C. , Serban Monica A.
Published: September 2022

Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed a tetraethyl orthosilicate-based hydrogel for use as single application treatment for otitis externa to increase ease of use and improve patient outcomes. Herein, we investigated the manufacturability of the hydrogel, focusing on several key aspects: formulation repeatability and reproducibility, material source and tolerances, release of a variety of model drugs, and impact of application-specific physiological factors, specifically local pH and enzymatic activity on drug release. Overall, our results indicate that these hydrogels are well suited for production and scalability, as they have a robust manufacturing process, have a wide tolerance for pH level, release a variety of model drugs, and are not impacted by outer ear canal-specific physiological factors.
Development of a Novel Lipid-Based Nanosystem Functionalized with WGA for Enhanced Intracellular Drug Delivery
Authors: Hädrich Gabriela , Vaz Gustavo Richter , Bidone Juliana , Yurgel Virginia Campello , Teixeira Helder Ferreira , Gonçalves Dal Bó Alexandre , da Silva Pinto Luciano , Hort Mariana Appel , Ramos Daniela Fernandes , Junior Antonio Sergio Varela , Almeida da Silva Pedro Eduardo , Dora Cristiana Lima
Published: September 2022

Despite a considerable number of new antibiotics under going clinical trials, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The use of lipid nanocarriers provides several advantages such as protection from compound degradation, increased bioavailability, and controlled and targeted drug release. Wheat germ agglutinin (WGA) is known to have its receptors on the alveolar epithelium and increase phagocytosis. The present study aimed to produce nanostructured lipid carriers with novel glycosylated amphiphilic employed to attach WGA on the surface of the nanocarriers to improve intracellular drug delivery. High-pressure homogenization was employed to prepare the lipid nanocarriers. In vitro, high-content analysis and flow cytometry assay was employed to study the increased uptake by macrophages when the nanocarriers were grafted with WGA. A lipid nanocarrier with surface-functionalized WGA protein (~200 nm, PDI > 0.3) was successfully produced and characterized. The system was loaded with a lipophilic model compound (quercetin; QU), demonstrating the ability to encapsulate a high amount of compound and release it in a controlled manner. The nanocarrier surface functionalization with the WGA protein increased the phagocytosis by macrophages. The system proposed here has characteristics to be further explored to treat intracellular pathogens.
Applications of Exosomes in Diagnosing Muscle Invasive Bladder Cancer
Authors: Walker Jillian Marie , O’Malley Padraic , He Mei
Published: September 2022

Muscle Invasive Bladder Cancer (MIBC) is a subset of bladder cancer with a significant risk for metastases and death. It accounts for nearly 25% of bladder cancer diagnoses. A diagnostic work-up for MIBC is inclusive of urologic evaluation, radiographic imaging with a CT scan, urinalysis, and cystoscopy. These evaluations, especially cystoscopy, are invasive and carry the risk of secondary health concerns. Non-invasive diagnostics such as urine cytology are an attractive alternative currently being investigated to mitigate the requirement for cystoscopy. A pitfall in urine cytology is the lack of available options with high reliability, specificity, and sensitivity to malignant bladder cells. Exosomes are a novel biomarker source which could resolve some of the concerns with urine cytology, due to the high specificity as the surrogates of tumor cells. This review serves to define muscle invasive bladder cancer, current urine cytology methods, the role of exosomes in MIBC, and exosomes application as a diagnostic tool in MIBC. Urinary exosomes as the specific populations of extracellular vesicles could provide additional biomarkers with specificity and sensitivity to bladder malignancies, which are a consistent source of cellular information to direct clinicians for developing treatment strategies. Given its strong presence and differentiation ability between normal and cancerous cells, exosome-based urine cytology is highly promising in providing a perspective of a patient’s bladder cancer.
Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy
Authors: Hou Wanting , Yang Biao , Zhu Hong
Published: September 2022

Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applications in improving drug delivery and reversing the immunosuppressive TME for PDAC. Therefore, nanomaterial-based therapeutic approaches are expected to enhance the effectiveness of immunotherapy and improve prognosis of patients with PDAC. Here, we outline the status and dilemma of PDAC immunotherapy, and summarize the latest advances in nanoparticle-based treatment strategies to enhance the efficacy of PDAC immunotherapy.
Multiplex Analysis of CircRNAs from Plasma Extracellular Vesicle-Enriched Samples for the Detection of Early-Stage Non-Small Cell Lung Cancer
Authors: Pedraz-Valdunciel Carlos , Giannoukakos Stavros , Giménez-Capitán Ana , Fortunato Diogo , Filipska Martyna , Bertran-Alamillo Jordi , Bracht Jillian W. P. , Drozdowskyj Ana , Valarezo Joselyn , Zarovni Natasa , Fernández-Hilario Alberto , Hackenberg Michael , Aguilar-Hernández Andrés , Molina-Vila Miguel Ángel , Rosell Rafael
Published: September 2022

Background: The analysis of liquid biopsies brings new opportunities in the precision oncology field. Under this context, extracellular vesicle circular RNAs (EV-circRNAs) have gained interest as biomarkers for lung cancer (LC) detection. However, standardized and robust protocols need to be developed to boost their potential in the clinical setting. Although nCounter has been used for the analysis of other liquid biopsy substrates and biomarkers, it has never been employed for EV-circRNA analysis of LC patients. Methods: EVs were isolated from early-stage LC patients (n = 36) and controls (n = 30). Different volumes of plasma, together with different number of pre-amplification cycles, were tested to reach the best nCounter outcome. Differential expression analysis of circRNAs was performed, along with the testing of different machine learning (ML) methods for the development of a prognostic signature for LC. Results: A combination of 500 μL of plasma input with 10 cycles of pre-amplification was selected for the rest of the study. Eight circRNAs were found upregulated in LC. Further ML analysis selected a 10-circRNA signature able to discriminate LC from controls with AUC ROC of 0.86. Conclusions: This study validates the use of the nCounter platform for multiplexed EV-circRNA expression studies in LC patient samples, allowing the development of prognostic signatures.
Biological Evaluation of the Effect of Root Canal Sealers Using a Rat Model
Authors: Okamoto Motoki , Matsumoto Sayako , Moriyama Kiichi , Huang Hailing , Watanabe Masakatsu , Miura Jiro , Sugiyama Keita , Hirose Yujiro , Mizuhira Manabu , Kuriki Nanako , Leprince Julian G. , Takahashi Yusuke , Kawabata Shigetada , Hayashi Mikako
Published: September 2022

Gutta-percha points and root canal sealers have been used for decades in endodontics for root canal obturation. With techniques such as single cone methods, the amount of sealer is larger, making their properties more critical. However, relatively few reports have comprehensively evaluated their biological effects. To this end, we evaluated three types of sealers, zinc oxide-fatty acid-, bio-glass- and methacrylate resin-containing sealers were considered. Their biological effects were evaluated using a rat subcutaneous implantation model. Each sealer was loaded inside a Teflon tube and implanted subcutaneously in the backs of rats. Inflammatory cells were observed around all samples 7 days after implantation and reduced after 28 days. Our results revealed that all samples were in contact with the subcutaneous tissue surrounding the sealer. Additionally, Ca and P accumulation was observed in only the bio-glass-containing sealer. Furthermore, each of the three sealers exhibited unique immune and inflammatory modulatory effects. In particular, bio-glass and methacrylate resin sealers were found to induce variable gene expression in adjacent subcutaneous tissues related to angiogenesis, wound healing, muscle tissue, and surrounding subcutaneous tissue. These results may help to understand the biological impacts of root canal sealers on surrounding biological tissues, guiding future research and comparisons with new generations of materials.
Positron Emission Tomography Probes for Imaging Cytotoxic Immune Cells
Authors: Amgheib Ala , Fu Ruisi , Aboagye Eric O.
Published: September 2022

Non-invasive positron emission tomography (PET) imaging of immune cells is a powerful approach for monitoring the dynamics of immune cells in response to immunotherapy. Despite the clinical success of many immunotherapeutic agents, their clinical efficacy is limited to a subgroup of patients. Conventional imaging, as well as analysis of tissue biopsies and blood samples do not reflect the complex interaction between tumour and immune cells. Consequently, PET probes are being developed to capture the dynamics of such interactions, which may improve patient stratification and treatment evaluation. The clinical efficacy of cancer immunotherapy relies on both the infiltration and function of cytotoxic immune cells at the tumour site. Thus, various immune biomarkers have been investigated as potential targets for PET imaging of immune response. Herein, we provide an overview of the most recent developments in PET imaging of immune response, including the radiosynthesis approaches employed in their development.