bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence-Based Recommendations for an Optimal Prenatal Supplement for Women in the U.S., Part Two: Minerals
Authors: Adams James B. , Sorenson Jacob C. , Pollard Elena L. , Kirby Jasmine K. , Audhya Tapan
Published: May 2021

The levels of many essential minerals decrease during pregnancy if un-supplemented, including calcium, iron, magnesium, selenium, zinc, and possibly chromium and iodine. Sub-optimal intake of minerals from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of minerals is often below the Recommended Dietary Allowance (RDA), especially for iodine and magnesium, and 28% of women develop iron deficiency anemia during their third trimester. The goal of this paper is to propose evidence-based recommendations for the optimal level of prenatal supplementation for each mineral for most women in the United States. Overall, the evidence suggests that optimal mineral supplementation can significantly reduce a wide range of pregnancy complications (including anemia, gestational hypertension, gestational diabetes, hyperthyroidism, miscarriage, and pre-eclampsia) and infant health problems (including anemia, asthma/wheeze, autism, cerebral palsy, hypothyroidism, intellectual disability, low birth weight, neural tube defects, preterm birth, rickets, and wheeze). An evaluation of 180 commercial prenatal supplements found that they varied widely in mineral content, often contained only a subset of essential minerals, and the levels were often below our recommendations. Therefore, there is a need to establish recommendations on the optimal level of mineral supplementation during pregnancy.
Dietary Intake of n-3 PUFA-Enriched Hen Eggs Changes Inflammatory Markers’ Concentration and Treg/Th17 Cells Distribution in Blood of Young Healthy Adults—A Randomised Study
Authors: Kolobarić Nikolina , Drenjančević Ines , Matić Anita , Šušnjara Petar , Mihaljević Zrinka , Mihalj Martina
Published: May 2021

In the present study, we aimed to determine the effects of n-3 polyunsaturated acid (PUFA) supplementation (~1053 mg/per day), i.e., α-linolenic (~230 mg), eicosapentaenoic (~15 mg), and docosahexaenoic acid (~105 mg), through hen eggs, on pro- and anti-inflammatory parameters in healthy individuals (23.8 ± 2.57 years old). Here, we demonstrate differential effects of regular hen eggs (N = 21; W/M = 10/11) and n-3 PUFA-enriched hen eggs (N = 19; W/M = 10/9) consumption on the serum levels of lipid mediators, representation of peripheral T helper cell subsets (recently activated T-helper cells, nTreg, Th17 and non-Th17-IL-17A secreting T-helper lymphocytes) and their functional capacity for cytokine secretion. Both diets significantly altered systemic levels of pro-inflammatory and inflammation resolving lipid mediators; however, only the n-3 PUFAs group showed a significant shift towards anti-inflammatory prostanoids and increased levels of pro-resolving oxylipins. Both study groups showed reduced frequencies of peripheral nTreg lymphocytes and decreased rates of peripheral Th17 cells. Their functional capacity for cytokine secretion was significantly altered only in the n-3 PUFAs group in terms of increased transforming growth factor β-1 and reduced interleukin 6 secretion. Diet supplemented with n-3 PUFAs alters immune response towards inflammation resolving conditions through effects on lipid mediators and cytokine secretion by T lymphocytes in human model without underlying comorbidities.
Diet Quality Is Associated with a High Newborn Size and Reduction in the Risk of Low Birth Weight and Small for Gestational Age in a Group of Mexican Pregnant Women: An Observational Study
Authors: Reyes-López María A. , González-Leyva Carla P. , Rodríguez-Cano Ameyalli M. , Rodríguez-Hernández Carolina , Colin-Ramírez Eloisa , Estrada-Gutierrez Guadalupe , Muñoz-Manrique Cinthya G. , Perichart-Perera Otilia
Published: May 2021

A high-quality diet during pregnancy may have positive effects on fetal growth and nutritional status at birth, and it may modify the risk of developing chronic diseases later in life. The aim of this study was to evaluate the association between diet quality and newborn nutritional status in a group of pregnant Mexican women. As part of the ongoing Mexican prospective cohort study, OBESO, we studied 226 healthy pregnant women. We adapted the Alternated Healthy Eating Index-2010 for pregnancy (AHEI-10P). The association between maternal diet and newborn nutritional status was investigated by multiple linear regression and logistic regression models. We applied three 24-h recalls during the second half of gestation. As the AHEI-10P score improved by 5 units, the birth weight and length increased (β = 74.8 ± 35.0 g and β = 0.3 ± 0.4 cm, respectively, p < 0.05). Similarly, the risk of low birth weight (LBW) and small for gestational age (SGA) decreased (OR: 0.47, 95%CI: 0.27–0.82 and OR: 0.55, 95%CI: 0.36–0.85, respectively). In women without preeclampsia and/or GDM, the risk of stunting decreased as the diet quality score increased (+5 units) (OR: 0.62, 95%IC: 0.40–0.96). A high-quality diet during pregnancy was associated with a higher newborn size and a reduced risk of LBW and SGA in this group of pregnant Mexican women.
Expanded Role of a Dietitian in Monitoring a Gluten-Free Diet in Patients with Celiac Disease: Implications for Clinical Practice
Authors: Gładyś Katarzyna , Dardzińska Jolanta , Guzek Marek , Adrych Krystian , Kochan Zdzisław , Małgorzewicz Sylwia
Published: May 2021

Access to a registered dietitian experienced in celiac disease (CD) is still limited, and consultation when available focuses primarily on the elimination of gluten from the diet. Thus, the aim of this study was to evaluate the nutritional value of a gluten-free diet (GFD) in adult CD patients before, and one year after, the standard dietary education. The study included 72 CD patients on a GFD and 30 healthy controls. The dietary intake of both groups was assessed through a 3-day food diary, while adherence to a GFD in celiac subjects was assessed using Standardized Dietician Evaluation (SDE). Subsequently, all CD patients received detailed education on gluten sources, and 48 of them participated in a one-year follow-up. Results: Comparison with the control group showed that consumption of plant protein in CD patients was significantly lower, whereas fat and calories were higher. At baseline, only 62% of CD patients adhered to a GFD, but the standard dietary education successfully improved it. However, the nutritional value of a GFD after one year did not change, except for a reduced sodium intake. The CD subjects still did not consume enough calcium, iron, vitamin D, folic acid or fiber. In conclusion, while the standard dietary education improved GFD adherence, it did not significantly alter its nutritional value. Therefore, it is necessary to increase the role of a dietitian in the treatment of CD.
The Use of Non-Nutritive and Low-Calorie Sweeteners in 19,915 Local and Imported Pre-Packaged Foods in Hong Kong
Authors: O Billy Yin Sing , Coyle Daisy H. , Dunford Elizabeth K. , Wu Jason H. Y. , Louie Jimmy Chun Yu
Published: May 2021

This study aims to examine the use of non-nutritive (NNSs) and low-calorie sweeteners (LCSs) in pre-packaged foods in Hong Kong and the differences in the number of NNSs/LCSs used between products from different regions. In a cross-sectional audit, the types of NNSs/LCSs used in 19,915 pre-packaged foods in Hong Kong were examined by searching the ingredients list of the included products for keywords related to 20 common NNSs/LCSs and their respective E-numbers. Prevalence of use of NNSs and LCSs, the co-presence of NNSs/LCSs and free sugar ingredients (FSI), and the number of NNSs/LCSs used in the included foods were computed. Pearson’s χ2 test was used to compare the total number of NNSs and/or LCSs used in food items from different regions. Sucralose (E955) was the most commonly used NNS (1.9%), followed by acesulfame K (E950, 1.6%). Sorbitol was the most commonly used LCS (2.9%). Overall, the use of LCSs was less common compared with NNSs (3.7% vs. 4.5%). The use of different types of NNSs varied substantially between food types. Notably, 20.2% of potato crisps and 15.2% of other crisps or extruded snacks contained at least one NNS and/or LCS. Co-presence of FSIs and NNSs/LCSs were most common in confectionery (15.7%) and snack foods (15.5%). Asian prepackaged foods were more likely to contain NNSs/LCSs (10.1%) compared with those from other regions. To conclude, NNSs/LCSs were used in a wide range of non-diet pre-packaged products which could be a public health concern due to their higher consumption frequencies than “diet” products.
Associations of Lifestyle Factors with Osteopenia and Osteoporosis in Polish Patients with Inflammatory Bowel Disease
Authors: Rychter Anna Maria , Ratajczak Alicja Ewa , Szymczak-Tomczak Aleksandra , Michalak Michał , Eder Piotr , Dobrowolska Agnieszka , Krela-Kaźmierczak Iwona
Published: May 2021

Reduced physical activity (PA), smoking, and coffee and alcohol drinking constitute risk factors of osteoporosis in patients with inflammatory bowel disease (IBD). The aim of the study was to measure the bone mineral density (BMD) and frequency of osteopenia and osteoporosis in patients with IBD and their correlation with PA, smoking, coffee, and alcohol. The study group consisted of 208 patients with IBD-103 with Crohn’s disease (CD), 105 suffering from ulcerative colitis (UC). Densitometric measurements were performed using the DXA. All patients completed a questionnaire concerning PA, smoking, and coffee and alcohol consumption. The prevalence of osteopenia and osteoporosis (L2–L4) in the IBD group was 48.1%; in the CD group, it amounted to 48.6%, and in the UC group, the prevalence was equal to 33.3%. Patients with CD who were diagnosed with osteopenia and osteoporosis demonstrated reduced PA compared to patients with a normal BMD who exercised regularly (p = 0.0335). A similar observation was made in the group of women with IBD. Women with a normal BMD exercised significantly more often than women suffering from osteopenia and osteoporosis (p = 0.0146). However, no differences in BMD were observed with regard to coffee use, alcohol consumption, or smoking. Thus, since the incidence of osteoporosis in IBD patients is high, it may be dependent on PA.
Changes in Fatty Acid Dietary Profile Affect the Brain–Gut Axis Functions of Healthy Young Adult Rats in a Sex-Dependent Manner
Authors: Jacenik Damian , Bagüés Ana , López-Gómez Laura , López-Tofiño Yolanda , Iriondo-DeHond Amaia , Serra Cristina , Banovcanová Laura , Gálvez-Robleño Carlos , Fichna Jakub , del Castillo Maria Dolores , Uranga José Antonio , Abalo Raquel
Published: May 2021

Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain–gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain–gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2–3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain–gut axis parameters were evaluated during 4–6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain–gut axis alterations in a sex-dependent manner, with a relatively higher risk in females.
Monosodium Glutamate Induces Changes in Hepatic and Renal Metabolic Profiles and Gut Microbiome of Wistar Rats
Authors: Nahok Kanokwan , Phetcharaburanin Jutarop , Li Jia V. , Silsirivanit Atit , Thanan Raynoo , Boonnate Piyanard , Joonhuathon Jarus , Sharma Amod , Anutrakulchai Sirirat , Selmi Carlo , Cha’on Ubon
Published: May 2021

The short- and long-term consumption of monosodium glutamate (MSG) increases urinary pH but the effects on the metabolic pathways in the liver, kidney and the gut microbiota remain unknown. To address this issue, we investigated adult male Wistar rats allocated to receive drinking water with or without 1 g% MSG for 2 weeks (n = 10, each). We performed a Nuclear Magnetic Resonance (NMR) spectroscopy-based metabolomic study of the jejunum, liver, and kidneys, while faecal samples were collected for bacterial DNA extraction to investigate the gut microbiota using 16S rRNA gene sequencing. We observed significant changes in the liver of MSG-treated rats compared to controls in the levels of glucose, pyridoxine, leucine, isoleucine, valine, alanine, kynurenate, and nicotinamide. Among kidney metabolites, the level of trimethylamine (TMA) was increased, and pyridoxine was decreased after MSG-treatment. Sequencing of the 16S rRNA gene revealed that MSG-treated rats had increased Firmicutes, the gut bacteria associated with TMA metabolism, along with decreased Bifidobacterium species. Our data support the impact of MSG consumption on liver and kidney metabolism. Based on the gut microbiome changes, we speculate that TMA and its metabolites such as trimethylamine-N-oxide (TMAO) may be mediators of the effects of MSG on the kidney health.
Dietary Phytochemicals in Zinc Homeostasis: A Strategy for Prostate Cancer Management
Authors: Singh Chandra K. , Chhabra Gagan , Patel Arth , Chang Hao , Ahmad Nihal
Published: May 2021

Studies have suggested an important role of the trace element zinc (Zn) in prostate biology and functions. Zn has been shown to exist in very high concentrations in the healthy prostate and is important for several prostatic functions. In prostate cancer (PCa), Zn levels are significantly decreased and inversely correlated with disease progression. Ideally, restoration of adequate Zn levels in premalignant/malignant prostate cells could abort prostate malignancy. However, studies have shown that Zn supplementation is not an efficient way to significantly increase Zn concentrations in PCa. Based on a limited number of investigations, the reason for the lower levels of Zn in PCa is believed to be the dysregulation of Zn transporters (especially ZIP and ZnT family of proteins), metallothioneins (for storing and releasing Zn), and their regulators (e.g., Zn finger transcription factor RREB1). Interestingly, the level of Zn in cells has been shown to be modulated by naturally occurring dietary phytochemicals. In this review, we discussed the effect of selected phytochemicals (quercetin, resveratrol, epigallocatechin-3-gallate and curcumin) on Zn functioning and proposes that Zn in combination with specific dietary phytochemicals may lead to enhanced Zn bioaccumulation in the prostate, and therefore, may inhibit PCa.
Prepubertal Dietary and Plasma Phospholipid Fatty Acids Related to Puberty Timing: Longitudinal Cohort and Mendelian Randomization Analyses
Authors: Cheng Tuck Seng , Day Felix R. , Perry John R. B. , Luan Jian’an , Langenberg Claudia , Forouhi Nita G. , Wareham Nicholas J. , Ong Ken K.
Published: May 2021

Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid FAs with several puberty timing traits in boys and girls. In the Avon Longitudinal Study of Parents and Children, prepubertal fat intakes at 3–7.5 years and plasma phospholipid FAs at 7.5 years were measured. Timings of Tanner stage 2 genital or breast development and voice breaking or menarche from repeated reports at 8–17 years, and age at peak height velocity (PHV) from repeated height measurements at 5–20 years were estimated. In linear regression models with adjustment for maternal and infant characteristics, dietary substitution of polyunsaturated FAs for saturated FAs, and higher concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier timing of puberty traits in girls (n = 3872) but not boys (n = 3654). In Mendelian Randomization models, higher genetically predicted circulating dihomo-γ-linolenic acid was associated with earlier menarche in girls. Based on repeated dietary intake data, objectively measured FAs and genetic causal inference, these findings suggest that dietary and endogenous metabolic pathways that increase plasma dihomo-γ-linolenic acid, an intermediate metabolite of n-6 polyunsaturated FAs, may promote earlier puberty timing in girls.
Fermented Rice Bran Supplementation Prevents the Development of Intestinal Fibrosis Due to DSS-Induced Inflammation in Mice
Authors: Agista Afifah Zahra , Rusbana Tubagus Bahtiar , Islam Jahidul , Ohsaki Yusuke , Sultana Halima , Hirakawa Ryota , Watanabe Kouichi , Nochi Tomonori , Ardiansyah  , Budijanto Slamet , Yang Suh-Ching , Koseki Takuya , Aso Hisashi , Komai Michio , Shirakawa Hitoshi
Published: May 2021

Fermented rice bran (FRB) is known to protect mice intestines against dextran sodium sulfate (DSS)-induced inflammation; however, the restoration of post-colitis intestinal homeostasis using FRB supplementation is currently undocumented. In this study, we observed the effects of dietary FRB supplementation on intestinal restoration and the development of fibrosis after DSS-induced colitis. DSS (1.5%) was introduced in the drinking water of mice for 5 days. Eight mice were sacrificed immediately after the DSS treatment ended. The remaining mice were divided into three groups, comprising the following diets: control, 10% rice bran (RB), and 10% FRB-supplemented. Diet treatment was continued for 2 weeks, after which half the population of mice from each group was sacrificed. The experiment was continued for another 3 weeks before the remaining mice were sacrificed. FRB supplementation could reduce the general observation of colitis and production of intestinal pro-inflammatory cytokines. FRB also increased intestinal mRNA levels of anti-inflammatory cytokine, tight junction, and anti-microbial proteins. Furthermore, FRB supplementation suppressed markers of intestinal fibrosis. This effect might have been achieved via the canonical Smad2/3 activation and the non-canonical pathway of Tgf-β activity. These results suggest that FRB may be an alternative therapeutic agent against inflammation-induced intestinal fibrosis.
Effect of Vitamin D Supplementation on Skeletal Muscle Volume and Strength in Patients with Decompensated Liver Cirrhosis Undergoing Branched Chain Amino Acids Supplementation: A Prospective, Randomized, Controlled Pilot Trial
Authors: Okubo Tomomi , Atsukawa Masanori , Tsubota Akihito , Ono Hiroki , Kawano Tadamichi , Yoshida Yuji , Arai Taeang , Hayama Korenobu , Itokawa Norio , Kondo Chisa , Kaneko Keiko , Iwakiri Katsuhiko
Published: May 2021

Background: Sarcopenia worsens patient prognoses in chronic liver disease. This study aimed to elucidate the effects of vitamin D supplementation on skeletal muscle volume and strength in patients with decompensated cirrhosis. Methods: Thirty-three patients were entered into the study based on the criteria and then randomly assigned to two groups: Group A (n = 17), the control group, and Group B (n = 16), those who received oral native vitamin D3 at a dose of 2000 IU once a day for 12 months. Results: SMI values in Group B were significantly increased at 12 months (7.64 × 10−3). The extent of changes in the SMI and grip strength in Group B were significantly greater than that in Group A at 12 months (p = 2.57 × 10−3 and 9.07 × 10−3). The median change rates in the SMI were +5.8% and the prevalence of sarcopenia was significantly decreased from 80.0% (12/15) to 33.3% (5/15; p = 2.53 × 10−2) in Group B. Conclusions: Vitamin D supplementation might be an effective and safe treatment option for patients with decompensated cirrhosis to increase or restore the skeletal muscle volume and strength or prevent the muscle volume and strength losses.
Daily Oral Supplementation with 60 mg of Elemental Iron for 12 Weeks Alters Blood Mitochondrial DNA Content, but Not Leukocyte Telomere Length in Cambodian Women
Authors: Steele Shannon L. , Hsieh Anthony Y. Y. , Gadawski Izabella , Kroeun Hou , Barr Susan I. , Devlin Angela M. , Côté Hélène C. F. , Karakochuk Crystal D.
Published: May 2021

There is limited evidence regarding the potential risk of untargeted iron supplementation, especially among individuals who are iron-replete or have genetic hemoglobinopathies. Excess iron exposure can increase the production of reactive oxygen species, which can lead to cellular damage. We evaluated the effect of daily oral supplementation on relative leukocyte telomere length (rLTL) and blood mitochondrial DNA (mtDNA) content in non-pregnant Cambodian women (18–45 years) who received 60 mg of elemental iron as ferrous sulfate (n = 190) or a placebo (n = 186) for 12 weeks. Buffy coat rLTL and mtDNA content were quantified by monochrome multiplex quantitative polymerase chain reaction. Generalized linear mixed-effects models were used to predict the absolute and percent change in rLTL and mtDNA content after 12 weeks. Iron supplementation was not associated with an absolute or percent change in rLTL after 12 weeks compared with placebo (ß-coefficient: −0.04 [95% CI: −0.16, 0.08]; p = 0.50 and ß-coefficient: −0.96 [95% CI: −2.69, 0.77]; p = 0.28, respectively). However, iron supplementation was associated with a smaller absolute and percent increase in mtDNA content after 12 weeks compared with placebo (ß-coefficient: −11 [95% CI: −20, −2]; p = 0.02 and ß-coefficient: −11 [95% CI: −20, −1]; p= 0.02, respectively). Thus, daily oral iron supplementation for 12 weeks was associated with altered mitochondrial homeostasis in our study sample. More research is needed to understand the risk of iron exposure and the biological consequences of altered mitochondrial homeostasis in order to inform the safety of the current global supplementation policy.
Association between Food Insecurity and Sarcopenia among Adults Aged ≥65 Years in Low- and Middle-Income Countries
Authors: Smith Lee , Jacob Louis , Barnett Yvonne , Butler Laurie T. , Shin Jae Il , López-Sánchez Guillermo F. , Soysal Pinar , Veronese Nicola , Haro Josep Maria , Koyanagi Ai
Published: May 2021

Limited literature has investigated the association between food insecurity and sarcopenia in low- and middle-income countries (LMICs). Therefore, the aim of the present study was to investigate the association between food insecurity and sarcopenia among adults aged ≥65 years in six LMICs. Community-based cross-sectional data of the Study on Global Ageing and Adult Health were analyzed. Sarcopenia was defined as the presence of low skeletal muscle mass based on indirect population formula, and either slow gait or low handgrip strength. In the past, 12-month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Multivariable logistic regression analysis was conducted. The final sample consisted of 14,585 individuals aged ≥65 years (mean (SD) age 72.6 (11.5) years; 55.0% females). The prevalence of sarcopenia among those with no food insecurity was 13.0% but this increased to 24.4% among those with severe food insecurity. After adjustment for potential confounders, compared to no food insecurity, severe food insecurity was associated with 2.05 (95%CI = 1.12–3.73) times higher odds for sarcopenia. In this large representative sample of older adults from multiple LMICs, it was found that severe food insecurity is associated with higher odds for sarcopenia. Addressing food insecurity in such settings may be an effective strategy to curb the high prevalence of sarcopenia in LMICs.
Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop
Authors: Baek Seung , Hammock Bruce , Hwang In-Koo , Li Qing , Moustaid-Moussa Naima , Park Yeonhwa , Safe Stephen , Suh Nanjoo , Yi Sun-Shin , Zeldin Darryl , Zhong Qixin , Bradbury Jennifer , Edin Matthew , Graves Joan , Jung Hyo-Young , Jung Young-Hyun , Kim Mi-Bo , Kim Woosuk , Lee Jaehak , Li Hong , Moon Jong-Seok , Yoo Ik-Dong , Yue Yiren , Lee Ji-Young , Han Ho-Jae
Published: May 2021

The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases.
Deconstructing the Supermarket: Systematic Ingredient Disaggregation and the Association between Ingredient Usage and Product Health Indicators for 24,229 Australian Foods and Beverages
Authors: Gaines Allison , Shahid Maria , Huang Liping , Davies Tazman , Taylor Fraser , Wu Jason HY , Neal Bruce
Published: May 2021

Unhealthy diets are underpinned by the over-consumption of packaged products. Data describing the ingredient composition of these products is limited. We sought to define the ingredients used in Australian packaged foods and beverages and assess associations between the number of ingredients and existing health indicators. Statements of ingredients were disaggregated, creating separate fields for each ingredient and sub-ingredient. Ingredients were categorised and the average number of ingredients per product was calculated. Associations between number of ingredients and both the nutrient-based Health Star Rating (HSR) and the NOVA level-of-processing classification were assessed. A total of 24,229 products, listing 233,113 ingredients, were included. Products had between 1 and 62 ingredients (median (Interquartile range (IQR)): 8 (3–14)). We identified 915 unique ingredients, which we organised into 17 major and 138 minor categories. ‘Additives’ were contained in the largest proportion of products (64.6%, (15,652/24,229)). The median number of ingredients per product was significantly lower in products with the optimum 5-star HSR (when compared to all other HSR score groups, p-value < 0.001) and significantly higher in products classified as ultra-processed (when compared to all other NOVA classification groups, p-value < 0.001). There is a strong relationship between the number of ingredients in a product and indicators of nutritional quality and level of processing.
Clinical Management of COVID-19: A Review of Pharmacological Treatment Options
Authors: Heustess Ashli , Allard Melissa , Thompson Dorothea , Fasinu Pius
Published: May 2021

Since the outbreak and subsequent declaration of COVID-19 as a global pandemic in March 2020, concerted efforts have been applied by the scientific community to curtail the spread of the disease and find a cure. While vaccines constitute a vital part of the public health strategy to reduce the burden of COVID-19, the management of this disease will continue to rely heavily on pharmacotherapy. This study aims to provide an updated review of pharmacological agents that have been developed and/or repurposed for the treatment of COVID-19. To this end, a comprehensive literature search was conducted using the PubMed, Google Scholar, and LitCovid databases. Relevant clinical studies on drugs used in the management of COVID-19 were identified and evaluated in terms of evidence of efficacy and safety. To date, the FDA has approved three therapies for the treatment of COVID-19 Emergency Use Authorization: convalescent plasma, remdesivir, and casirivimab/imdevimab (REGN-COV2). Drugs such as lopinavir/ritonavir, umifenovir, favipiravir, anakinra, chloroquine, hydroxychloroquine, tocilizumab, interferons, tissue plasminogen activator, intravenous immunoglobulins, and nafamosat have been used off-label with mixed therapeutic results. Adjunctive administration of corticosteroids is also very common. The clinical experience with these approved and repurposed drugs is limited, and data on efficacy for the new indication are not strong. Overall, the response of the global scientific community to the COVID-19 pandemic has been impressive, as evident from the volume of scientific literature elucidating the molecular biology and pathophysiology of SARS-CoV-2 and the approval of three new drugs for clinical management. Reviewed studies have shown mixed data on efficacy and safety of the currently utilized drugs. The lack of standard treatment for COVID-19 has made it difficult to interpret results from most of the published studies due to the risk of attribution error. The long-term effects of drugs can only be assessed after several years of clinical experience; therefore, the efficacy and safety of current COVID-19 therapeutics should continue to be rigorously monitored as part of post-marketing studies.
Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets
Authors: Zakowiecki Daniel , Frankiewicz Maja , Hess Tobias , Cal Krzysztof , Gajda Maciej , Dabrowska Justyna , Kubiak Bartlomiej , Paszkowska Jadwiga , Wiater Marcela , Hoc Dagmara , Garbacz Grzegorz , Haznar-Garbacz Dorota
Published: May 2021

Novel calcium phosphate-based starter pellets were used to develop a biphasic-release multiple-unit pellet system (MUPS) with diclofenac sodium as a model drug in the form of hard gelatin capsules. For comparative purposes, corresponding formulations based on the inert cores made of microcrystalline cellulose, sucrose and isomalt were prepared. The developed system consisted of two types of drug-layered pellets attaining different release patterns: delayed-release (enteric-coated) and extended-release. Dissolution characteristics were examined using both compendial and biorelevant methods, which reflected fed and fasting conditions. The results were collated with an equivalent commercial product but prepared with the direct pelletization technique.
Time-Resolved Effect of Interferon-Alpha 2a on Activities of Nuclear Factor Kappa B, Pregnane X Receptor and on Drug Disposition Genes
Authors: Theile Dirk , Wagner Lelia , Bay Cindy , Haefeli Walter Emil , Weiss Johanna
Published: May 2021

Interferon-alpha (IFN-α) is suggested to cause pharmacokinetic drug interactions by lowering expression of drug disposition genes through affecting the activities of nuclear factor kappa B (NF-ĸB) and pregnane X receptor (PXR). The time-resolved impact of IFN-α 2a (1000 U/mL; 5000 U/mL; 2 h to 30 h) on the activities of NF-ĸB and PXR and mRNA expression (5000 U/mL; 24 h, 48 h) of selected drug disposition genes and on cytochrome P450 (CYP3A4) activity in LS180 cells (5000 U/mL; 24 h, 48 h) was evaluated using luciferase-based reporter gene assays, reverse transcription polymerase chain reaction, and luminescence-based CYP3A4 activity assays. The cross-talk between NF-ĸB activation and PXR suppression was evaluated by NF-ĸB blockage (10 µM parthenolide). IFN-α 2a initially (2 h, 6 h) enhanced NF-ĸB activity 2-fold and suppressed PXR activity by 30%. mRNA of CYP3A4 was halved, whereas UGT1A1 was increased (1.35-fold) after 24 h. After 48 h, ABCB1 expression was increased (1.76-fold). CYP3A4 activity remained unchanged after 24 h, but was enhanced after 48 h (1.35-fold). IFN-α 2a demonstrated short-term suppressive effects on PXR activity and CYP3A4 mRNA expression, likely mediated by activated NF-ĸB. Longer exposure enhanced CYP3A4 activity. Clinical trials should evaluate the relevance by investigating the temporal effects of IFN-α on CYP3A4 using a sensitive marker substrate.
Development of Physiologically Based Pharmacokinetic Model for Orally Administered Fexuprazan in Humans
Authors: Jeong Yoo-Seong , Kim Min-Soo , Lee Nora , Lee Areum , Chae Yoon-Jee , Chung Suk-Jae , Lee Kyeong-Ryoon
Published: May 2021

Fexuprazan is a new drug candidate in the potassium-competitive acid blocker (P-CAB) family. As proton pump inhibitors (PPIs), P-CABs inhibit gastric acid secretion and can be used to treat gastric acid-related disorders such as gastroesophageal reflux disease (GERD). Physiologically based pharmacokinetic (PBPK) models predict drug interactions as pharmacokinetic profiles in biological matrices can be mechanistically simulated. Here, we propose an optimized and validated PBPK model for fexuprazan by integrating in vitro, in vivo, and in silico data. The extent of fexuprazan tissue distribution in humans was predicted using tissue-to-plasma partition coefficients in rats and the allometric relationships of fexuprazan distribution volumes (VSS) among preclinical species. Urinary fexuprazan excretion was minimal (0.29–2.02%), and this drug was eliminated primarily by the liver and metabolite formation. The fraction absorbed (Fa) of 0.761, estimated from the PBPK modeling, was consistent with the physicochemical properties of fexuprazan, including its in vitro solubility and permeability. The predicted oral bioavailability of fexuprazan (38.4–38.6%) was within the range of the preclinical datasets. The Cmax, AUClast, and time-concentration profiles predicted by the PBPK model established by the learning set were accurately predicted for the validation sets.
Activation of Deoxyribonuclease I by Nicotinamide as a New Strategy to Attenuate Tetracycline-Resistant Biofilms of Cutibacterium acnes
Authors: Shih Yi-Hsien , Liu Donald , Chen Yen-Chou , Liao Ming-Hsuan , Lee Woan-Ruoh , Shen Shing-Chuan
Published: May 2021

Biofilms of Cutibacterium (C.) acnes (formerly Propionibacterium acnes) are responsible for the persistence and antibiotic resistance of acne vulgaris. In addition to the standard treatments for acne vulgaris, a common adjunctive treatment is the topical administration of nicotinamide (NAM). However, the effects of NAM on biofilms of C. acnes have never been explored. This study comprehensively investigates the effects of NAM against biofilms of C. acnes using in vitro and in vivo approaches. The results showed that NAM potentiated the efficacy of suboptimal dosing of tetracycline against C. acnes. Moreover, NAM alone decreased the formation and increased the degradation of biofilms in C. acnes. The antibiofilm effect of NAM against C. acnes was further enhanced in combination with deoxyribonuclease (DNase) I, an enzyme with known antibiofilm properties. The computational molecular docking, surface plasmon resonance analysis, and enzymatic kinetic assay demonstrated that NAM binds to DNase I and accelerated its reaction. In conclusion, NAM activates DNase I to attenuate biofilms of C. acnes. This offers valuable insights into the strategies against biofilms that are worth elaborating on in other biofilm-related chronic cutaneous infections in the future.
Computational Study on Temperature Driven Structure–Function Relationship of Polysaccharide Producing Bacterial Glycosyl Transferase Enzyme
Authors: González-Faune Patricio , Sánchez-Arévalo Ignacio , Sarkar Shrabana , Majhi Krishnendu , Bandopadhyay Rajib , Cabrera-Barjas Gustavo , Gómez Aleydis , Banerjee Aparna
Published: May 2021

Glycosyltransferase (GTs) is a wide class of enzymes that transfer sugar moiety, playing a key role in the synthesis of bacterial exopolysaccharide (EPS) biopolymer. In recent years, increased demand for bacterial EPSs has been observed in pharmaceutical, food, and other industries. The application of the EPSs largely depends upon their thermal stability, as any industrial application is mainly reliant on slow thermal degradation. Keeping this in context, EPS producing GT enzymes from three different bacterial sources based on growth temperature (mesophile, thermophile, and hyperthermophile) are considered for in silico analysis of the structural–functional relationship. From the present study, it was observed that the structural integrity of GT increases significantly from mesophile to thermophile to hyperthermophile. In contrast, the structural plasticity runs in an opposite direction towards mesophile. This interesting temperature-dependent structural property has directed the GT–UDP-glucose interactions in a way that thermophile has finally demonstrated better binding affinity (−5.57 to −10.70) with an increased number of hydrogen bonds (355) and stabilizing amino acids (Phe, Ala, Glu, Tyr, and Ser). The results from this study may direct utilization of thermophile-origin GT as best for industrial-level bacterial polysaccharide production.
Effect of Solution Viscosity on the Precipitation of PSaMA in Aqueous Phase Separation-Based Membrane Formation
Authors: Nielen Wouter , Willott Joshua , Galicia Julia , de Vos Wiebe
Published: May 2021

Aqueous phase separation (APS) is a recently developed sustainable alternative to the conventional organic solvent based nonsolvent-induced phase separation (NIPS) method to prepare polymeric membranes. In APS, polyelectrolytes are precipitated from aqueous solutions through pH or salinity switches. Although APS differs from NIPS in the polymer and solvents, they share many tuning parameters. In this work, we investigate the APS-based preparation of membranes from poly(styrene-alt-maleic acid) (PSaMA) with a focus on acid concentration in the coagulation bath, and polymer and additive concentration in the casting solution. Nanofiltration membranes are prepared using significantly lower concentrations of acid: 0.3 M HCl compared to the 2 M of either acetic or phosphoric acid used in previous works. It is shown that higher polymer concentrations can be used to prevent defect formation in the top layer. In addition, acetic acid concentration also strongly affects casting solution viscosity and thus can be used to control membrane structure, where lower acetic acid concentrations can prevent the formation of macrovoids in the support structure. The prepared nanofiltration membranes exhibit a very low molecular weight cutoff (210 ± 40 dalton), making these sustainable membranes very relevant for the removal of contaminants of emerging concern. Understanding how the parameters described here affect membrane preparation and performance is essential to optimizing membranes prepared with APS towards this important application.
Hybrid Nanofibrous Membranes as a Promising Functional Layer for Personal Protection Equipment: Manufacturing and Antiviral/Antibacterial Assessments
Authors: Alshabanah Latifah Abdullah , Hagar Mohamed , Al-Mutabagani Laila A. , Abozaid Ghada M. , Abdallah Salwa M. , Shehata Nader , Ahmed Hoda , Hassanin Ahmed H.
Published: May 2021

In this research work, nanofibrous hybrids are manufactured, characterized, and assessed as active antiviral and antibacterial membranes. In more detail, both polyvinyl alcohol (PVA) and thermoplastic polyurethane (TPU) nanofibrous (NF) membranes and their composites with embedded silver nanoparticles (Ag NPs) are manufactured by an electrospinning process. Their morphological structures have been investigated by a scanning electron microscope (SEM) which revealed a homogenous distribution and almost beads-free fibers in all manufactured samples. Characterization with spectroscopic tools has been performed and proved the successful manufacturing of Ag-incorporated PVA and TPU hybrid nanofibers. The crystalline phase of the nanofibers has been determined using an X-ray diffractometer (XRD) whose patterns showed their crystalline nature at an angle value (2θ) of less than 20°. Subsequent screening of both antiviral and antibacterial potential activities of developed nanohybrid membranes has been explored against different viruses, including SARS-Cov-2 and some bacterial strains. As a novel approach, the current work highlights potential effects of several polymeric hybrids on antiviral and antibacterial activities particularly against SARS-Cov-2. Moreover, two types of polymers have been tested and compared; PVA of excellent biodegradable and hydrophilic properties, and TPU of excellent mechanical, super elasticity, hydrophobicity, and durability properties. Such extreme polymers can serve a wide range of applications such as PPE, filtration, wound healing, etc. Consequently, assessment of their antiviral/antibacterial activities, as host matrices for Ag NPs, is needed for different medical applications. Our results showed that TPU-Ag was more effective than PVA-Ag as HIV-1 antiviral nanohybrid as well as in deactivating spike proteins of SARS-Cov-2. Both TPU-Ag and PVA-Ag nanofibrous membranes were found to have superior antimicrobial performance by increasing Ag concentration from 2 to 4 wt.%. Additionally, the developed membranes showed acceptable physical and mechanical properties along with both antiviral and antibacterial activities, which can enable them to be used as a promising functional layer in Personal Protective Equipment (PPE) such as (surgical gowns, gloves, overshoes, hair caps, etc.). Therefore, the developed functional membranes can support the decrease of both coronavirus spread and bacterial contamination, particularly among healthcare professionals within their workplace settings.
Copolymerization of Phthalic Anhydride with Epoxides Catalyzed by Amine-Bis(Phenolate) Chromium(III) Complexes
Authors: Bukowski Wiktor , Bukowska Agnieszka , Sobota Aleksandra , Pytel Maciej , Bester Karol
Published: May 2021

The effect of ligand structure on the catalytic activity of amine-bis(phenolate) chromium(III) complexes in the ring-opening copolymerization of phthalic anhydride and a series epoxides was studied. Eight complexes differing in the donor-pendant group (R1) and substituents (R2) in phenolate units were examined as catalysts of the model reaction between phthalic anhydride and cyclohexane oxide in toluene. They were used individually or as a part of the binary catalytic systems with nucleophilic co-catalysts. The co-catalyst was selected from the following organic bases: PPh3, DMAP, 1-butylimidazole, or DBU. The binary catalytic systems turned out to be more active than the complexes used individually, and DMAP proved to be the best choice as a co-catalyst. When the molar ratio of [PA]:[epoxide]:[Cr]:[DMAP] = 250:250:1:1 was applied, the most active complex (R1-X = CH2NMe2, R2 = F) allowed to copolymerize phthalic anhydride with differently substituted epoxides (cyclohexene oxide, 4-vinylcyclohexene oxide, styrene oxide, phenyl glycidyl ether, propylene oxide, butylene oxide, and epichlorohydrin) within 240 min at 110 °C. The resulting polyesters were characterized by Mn up to 20.6 kg mol−1 and narrow dispersity, and they did not contain polyether units.
Porous Polymers from High Internal Phase Emulsions as Scaffolds for Biological Applications
Authors: Kramer Stanko , Cameron Neil R. , Krajnc Peter
Published: May 2021

High internal phase emulsions (HIPEs), with densely packed droplets of internal phase and monomers dispersed in the continuous phase, are now an established medium for porous polymer preparation (polyHIPEs). The ability to influence the pore size and interconnectivity, together with the process scalability and a wide spectrum of possible chemistries are important advantages of polyHIPEs. In this review, the focus on the biomedical applications of polyHIPEs is emphasised, in particular the applications of polyHIPEs as scaffolds/supports for biological cell growth, proliferation and tissue (re)generation. An overview of the polyHIPE preparation methodology is given and possibilities of morphology tuning are outlined. In the continuation, polyHIPEs with different chemistries and their interaction with biological systems are described. A further focus is given to combined techniques and advanced applications.
Synthesis and Characterization of a Bioconjugate Based on Oleic Acid and L-Cysteine
Authors: Vizcarra-Pacheco Marco , Ley-Flores María , Matrecitos-Burruel Ana Mizrahim , López-Esparza Ricardo , Fernández-Quiroz Daniel , Lucero-Acuña Armando , Zavala-Rivera Paul
Published: May 2021

One of the main challenges facing materials science today is the synthesis of new biodegradable and biocompatible materials capable of improving existing ones. This work focused on the synthesis of new biomaterials from the bioconjugation of oleic acid with L-cysteine using carbodiimide. The resulting reaction leads to amide bonds between the carboxylic acid of oleic acid and the primary amine of L-cysteine. The formation of the bioconjugate was corroborated by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and nuclear magnetic resonance (NMR). In these techniques, the development of new materials with marked differences with the precursors was confirmed. Furthermore, NMR has elucidated a surfactant structure, with a hydrophilic part and a hydrophobic section. Ultraviolet-visible spectroscopy (UV-Vis) was used to determine the critical micellar concentration (CMC) of the bioconjugate. Subsequently, light diffraction (DLS) was used to analyze the size of the resulting self-assembled structures. Finally, transmission electron microscopy (TEM) was obtained, where the shape and size of the self-assembled structures were appreciated.
Fabrication and Characterization of Cinnamaldehyde-Loaded Mesoporous Bioactive Glass Nanoparticles/PHBV-Based Microspheres for Preventing Bacterial Infection and Promoting Bone Tissue Regeneration
Authors: Chotchindakun Kittipat , Pekkoh Jeeraporn , Ruangsuriya Jetsada , Zheng Kai , Unalan Irem , Boccaccini Aldo R.
Published: May 2021

Polyhydroxybutyrate-co-hydroxyvalerate (PHBV) is considered a suitable polymer for drug delivery systems and bone tissue engineering due to its biocompatibility and biodegradability. However, the lack of bioactivity and antibacterial activity hinders its biomedical applications. In this study, mesoporous bioactive glass nanoparticles (MBGN) were incorporated into PHBV to enhance its bioactivity, while cinnamaldehyde (CIN) was loaded in MBGN to introduce antimicrobial activity. The blank (PHBV/MBGN) and the CIN-loaded microspheres (PHBV/MBGN/CIN5, PHBV/MBGN/CIN10, and PHBV/MBGN/CIN20) were fabricated by emulsion solvent extraction/evaporation method. The average particle size and zeta potential of all samples were investigated, as well as the morphology of all samples evaluated by scanning electron microscopy. PHBV/MBGN/CIN5, PHBV/MBGN/CIN10, and PHBV/MBGN/CIN20 significantly exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli in the first 3 h, while CIN releasing behavior was observed up to 7 d. Human osteosarcoma cell (MG-63) proliferation and attachment were noticed after 24 h cell culture, demonstrating no adverse effects due to the presence of microspheres. Additionally, the rapid formation of hydroxyapatite on the composite microspheres after immersion in simulated body fluid (SBF) during 7 d revealed the bioactivity of the composite microspheres. Our findings indicate that this system represents an alternative model for an antibacterial biomaterial for potential applications in bone tissue engineering.