bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Calcifediol on Physical Performance and Muscle Strength Parameters: A Systematic Review and Meta-Analysis
Authors: Barbagallo Mario , Veronese Nicola , Di Prazza Agnese , Pollicino Francesco , Carruba Luca , La Carrubba Anna , Dominguez Ligia J.
Published: May 2022

There is general agreement that optimal vitamin D status is necessary for bones, muscles, and general health, particularly in older adults, who are at higher risk of negative consequences of vitamin D deficiency, including sarcopenia; vitamin D supplementation is proposed as a potential intervention to mitigate sarcopenia. Several RCTs have reported that calcifediol (25(OH)D) was more potent than cholecalciferol in increasing plasma 25(OH)D. The present systematic review and meta-analysis aimed to summarize the effects of calcifediol on physical performance and muscle strength. We searched databases from inception to 1 January 2022 for studies investigating calcifediol on physical performance or muscle strength parameters. We calculated the difference between the means of follow-up vs. baseline data using standardized mean differences (SMD) and their 95% confidence intervals (CIs); a random-effect model was considered for all of the analyses. Seven RCTs were included in the meta-analysis. Calcifediol significantly improved gait speed (SMD = 2.500; 95%CI = 1.768–3.223; p < 0.0001); handgrip strength (n = 5446 participants, SMD = 0.532; 95%CI: 0.305–0.758; p < 0.0001; I2 = 20.2%); and leg extension (n = 4318 participants, SMD = 0.641; 95%CI: 0.346 to 0.935; p < 0.0001; I2 = 18.8%;) vs. baseline values. In conclusion, in this systematic review and meta-analysis, we observed that calcifediol may have a positive effect on muscle strength parameters, with less evidence on physical performance. These data further indicate the importance of vitamin D and, in particular, of calcifediol, not only on bone metabolism but also on muscle parameters and sarcopenia.
miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
Authors: Gan Mailin , Ma Jianfeng , Chen Jingyun , Chen Lei , Zhang Shunhua , Zhao Ye , Niu Lili , Li Xuewei , Zhu Li , Shen Linyuan
Published: May 2022

Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle atrophy. Previous studies have shown beneficial effects of genistein treatment on muscle mass and muscle atrophy, but the mechanism is not fully understood. Differential co-expression network analysis revealed that miR-222 was upregulated in multiple skeletal muscle atrophy models. Subsequent in vitro (C2C12 myoblasts) and in vivo (C57BL/6 mice) experiments showed that genistein could alleviate dexamethasone-induced muscle atrophy and downregulate the expression of miR-222 in muscle tissue and C2C12 myotubes. The dual-luciferase reporter assay system confirmed that IGF1 is a target gene of miR-222 and is regulated by genistein. In C2C12 myotubes, both dexamethasone and miR-222 overexpression promoted muscle atrophy, however, this function was significantly reduced after genistein treatment. Furthermore, we also observed that both genistein and miR-222 antagomiR could significantly inhibit dexamethasone-induced muscle atrophy in vivo. These results suggest that miR-222 may be involved in the regulation of genistein on muscle atrophy, and genistein and miR-222 may be used to improve muscle health.
Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study
Authors: Voelkle Manyola , Gregoriano Claudia , Neyer Peter , Koch Daniel , Kutz Alexander , Bernasconi Luca , Conen Anna , Mueller Beat , Schuetz Philipp
Published: May 2022

Background: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. Methods: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. Results: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05–0.69, p = 0.01), zinc (0.73, 95% CI 0.55–0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78–0.98, p = 0.02). Conclusions: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.
The Relationship between Habitual Coffee Drinking and the Prevalence of Metabolic Syndrome in Taiwanese Adults: Evidence from the Taiwan Biobank Database
Authors: Lu Meng-Ying , Cheng Hsiao-Yang , Lai Jerry Cheng-Yen , Chen Shaw-Ji
Published: May 2022

Previous studies revealed inconsistent results between coffee drinking and metabolic syndrome (MetS). The aim of the study was to evaluate the relationship between habitual coffee drinking and the prevalence of MetS among men and women. We conducted a nationwide, cross-sectional study using 23,073 adults obtained from the Taiwan Biobank database (mean ± SD (range) age, 54.57 ± 0.07 (30–79) years; 8341 men and 14,731 (63.8%) women). Adults who drank more than one cup of coffee per day (n = 5118) and those who drank less than one cup per day (n = 4515) were compared with nondrinkers (n = 13,439). Multivariate logistic regression models were used to evaluate the risk of MetS between the two groups. Separate models were also estimated for sex-stratified and habitual coffee-type-stratified (black coffee (BC), coffee with creamer (CC), and coffee with milk (CM)) subgroup analyses. The MetS diagnosis was based on at least three of the five metabolic abnormalities. Coffee drinkers (≥1 cup/day) had a significantly lower prevalence of MetS than nondrinkers (AOR (95% CI): 0.80 (0.73–0.87)). Women who drank any amount of coffee and any type of coffee were more likely to have a significantly lower prevalence of MetS than nondrinkers. Only men who drank more than one cup of coffee per day or black coffee drinkers were more likely to have a lower prevalence of MetS. Our study results indicate that adults with habitual coffee drinking behaviors of more than one cup per day were associated with a lower prevalence of MetS. Moreover, women could benefit from habitual coffee drinking of all three coffee types, whereas men could only benefit from drinking BC.
Prenatal Choline Supplementation Alters One Carbon Metabolites in a Rat Model of Periconceptional Alcohol Exposure
Authors: Steane Sarah E. , Kumar Vinod , Cuffe James S. M. , Moritz Karen M. , Akison Lisa K.
Published: May 2022

Prenatal alcohol exposure disturbs fetal and placental growth and can alter DNA methylation (DNAm). Supplementation with the methyl donor choline can increase fetal and placental growth and restore DNAm, suggesting converging effects on one-carbon metabolism (1CM). We investigated the impact of periconceptional ethanol (PCE) exposure and prenatal choline supplementation on 1CM in maternal, placental, and fetal compartments. Female Sprague Dawley rats were given a liquid diet containing 12.5% ethanol (PCE) or 0% ethanol (control) for 4 days before and 4 days after conception. Dams were then placed on chow with different concentrations of choline (1.6 g, 2.6 g, or 7.2 g choline/kg chow). Plasma and tissues were collected in late gestation for the analysis of 1CM components by means of mass spectrometry and real-time PCR. PCE reduced placental components of 1CM, particularly those relating to folate metabolism, resulting in a 3–7.5-fold reduction in the ratio of s-adenosylmethionine:s-adenosylhomocysteine (SAM:SAH) (p < 0.0001). Choline supplementation increased placental 1CM components and the SAM:SAH ratio (3.5–14.5-fold, p < 0.0001). In the maternal and fetal compartments, PCE had little effect, whereas choline increased components of 1CM. This suggests that PCE impairs fetal development via altered placental 1CM, highlighting its role in modulating nutritional inputs to optimize fetal development.
Body Mass Index and the Risk of Atrial Fibrillation: A Mendelian Randomization Study
Authors: Ma Mi , Zhi Hong , Yang Shengyi , Yu Evan Yi-Wen , Wang Lina
Published: May 2022

Although observational studies have shown positive associations between body mass index (BMI) and the risk of atrial fibrillation (AF), the causal relationship is still uncertain owing to the susceptibility to confounding and reverse causation. This study aimed to examine the potential causality of BMI on AF by conducting a two-sample Mendelian randomization (TSMR) study. Methods: The independent genetic variants associated with BMI (n = 303) at the genome-wide significant level were derived as instrumental variables (IV) from the Genetic Investigation of Anthropometric Traits (GIANT) consortium consisting of 681,275 individuals of European ancestry. We then derived the outcome data from a GWAS meta-analysis comprised of 60,620 cases and 970,216 controls of European ancestry. The TSMR analyses were performed in five methods, namely inverse variance weighted (IVW) method, MR-Egger regression, the weighted median estimator (WME), the generalized summary data-based Mendelian randomization (GSMR), and the robust adjusted profile score (RAPS), to investigate whether BMI was causally associated with the risk of AF. Results: We found a genetically determined 1–standard deviation (SD) increment of BMI causally increased a 42.5% risk of AF (OR = 1.425; 95% CI, 1.346 to 1.509) based on the IVW method, which was consistent with the results of MR-Egger regression, WME, GSMR, as well as RAPS. The Mendelian randomization assumptions did not seem to be violated. Conclusion: This study provides evidence that higher BMI causally increased the risk of AF, suggesting control of BMI and obesity for prevention of AF.
Oral Supplement Containing Hydroxytyrosol and Punicalagin Improves Dyslipidemia in an Adult Population without Co-Adjuvant Treatment: A Randomized, Double-Blind, Controlled and Crossover Trial
Authors: Quirós-Fernández Rebeca , López-Plaza Bricia , Bermejo Laura M. , Palma Milla Samara , Zangara Andrea , Candela Carmen Gómez
Published: May 2022

Hydroxytyrosol (HT) and punicalagin (PC) exert cardioprotective and antiatherosclerotic effects. This study evaluated the effect of an oral supplement containing HT and PC (SAx) on dyslipidemia in an adult population. A randomized, double-blind, controlled, crossover trial was conducted over a 20-week period. SAx significantly reduced the plasma levels of triglycerides (TG) in subjects with hypertriglyceridemia (≥150 mg/dL) (from 200.67 ± 51.38 to 155.33 ± 42.44 mg/dL; p < 0.05), while no such effects were observed in these subjects after the placebo. SAx also significantly decreased the plasma levels of low-density lipoprotein cholesterol (LDL-C) in subjects with high plasma levels of LDL-C (≥160 mg/dL) (from 179.13 ± 16.18 to 162.93 ± 27.05 mg/dL; p < 0.01), while no such positive effect was observed with the placebo. In addition, the placebo significantly reduced the plasma levels of high-density lipoprotein cholesterol (HDL-C) in the total population (from 64.49 ± 12.65 to 62.55 ± 11.57 mg/dL; p < 0.05), while SAx significantly increased the plasma levels of HDL-C in subjects with low plasma levels of HDL-C (<50 mg/dL) (from 44.25 ± 3.99 to 48.00 ± 7.27 mg/dL; p < 0.05). In conclusion, the supplement containing HT and PC exerted antiatherosclerotic and cardio-protective effects by considerably improving dyslipidemia in an adult population, without co-adjuvant treatment or adverse effects.
Effect of Vitamin C and Protein Supplementation on Plasma Nitrate and Nitrite Response following Consumption of Beetroot Juice
Authors: Miller Gary D. , Nesbit Beverly A. , Kim-Shapiro Daniel B. , Basu Swati , Berry Michael J.
Published: May 2022

Beetroot juice is a food high in nitrate and is associated with cardiometabolic health benefits and enhanced exercise performance through the production of nitric oxide in the nitrate–nitrite–nitric oxide pathway. Since various food components influence this pathway, the aim of this trial was to study the effect of beetroot juice alone and in conjunction with vitamin C or protein on the acute response to plasma nitrate and nitrite levels in healthy middle- to older-aged adults. In this cross-over trial, each participant received, in a randomized order, a single dose of Beet It Sport® alone; Beet It Sport®, plus a 200 mg vitamin C supplement; and Beet It Sport® plus 15 g of whey protein. Plasma levels of nitrate and nitrite were determined prior to and at 1 and 3 h after intervention. Log plasma nitrate and nitrite was calculated to obtain data that were normally distributed, and these data were analyzed using two-way within-factors ANOVA, with time and treatment as the independent factors. There were no statistically significant differences for log plasma nitrate (p = 0.308) or log plasma nitrite (p = 0.391) values across treatments. Log plasma nitrate increased significantly from pre-consumption levels after 1 h (p < 0.001) and 3 h (p < 0.001), but plasma nitrate was lower at 3 h than 1 h (p < 0.001). Log plasma nitrite increased from pre to 1 h (p < 0.001) and 3 h (p < 0.001) with log values at 3 h higher than at 1 h (p = 0.003). In this cohort, we observed no differences in log plasma nitrate and nitrite at 1 h and 3 h after co-ingesting beetroot juice with vitamin C or a whey protein supplement compared to beetroot juice alone. Further research needs to be undertaken to expand the blood-sampling time-frame and to examine factors that may influence the kinetics of the plasma nitrate to nitrite efficacy, such as differences in fluid volume and osmolarity between treatments employed.
HDHL-INTIMIC: A European Knowledge Platform on Food, Diet, Intestinal Microbiomics, and Human Health
Authors: Agamennone Valeria , Abuja Peter M. , Basic Marijana , De Angelis Maria , Gessner André , Keijser Bart , Larsen Martin , Pinart Mariona , Nimptsch Katharina , Pujos-Guillot Estelle , Schlicht Kristina , Sharon Itai , Untersmayr Eva , Laudes Matthias , Pischon Tobias , Bouwman Jildau ,   on behalf of the Consortium
Published: May 2022

Studies indicate that the intestinal microbiota influences general metabolic processes in humans, thereby modulating the risk of chronic diseases such as type 2 diabetes, allergy, cardiovascular disease, and colorectal cancer (CRC). Dietary factors are also directly related to chronic disease risk, and they affect the composition and function of the gut microbiota. Still, detailed knowledge on the relation between diet, the microbiota, and chronic disease risk is limited. The overarching aim of the HDHL-INTIMIC (INtesTInal MICrobiomics) knowledge platform is to foster studies on the microbiota, nutrition, and health by assembling available knowledge of the microbiota and of the other aspects (e.g., food science and metabolomics) that are relevant in the context of microbiome research. The goal is to make this information findable, accessible, interoperable, and reusable (FAIR) to the scientific community, and to share information with the various stakeholders. Through these efforts a network of transnational and multidisciplinary collaboration has emerged, which has contributed to further develop and increase the impact of microbiome research in human health. The roles of microbiota in early infancy, during ageing, and in subclinical and clinically manifested disease are identified as urgent areas of research in this knowledge platform.
Piceatannol SNEDDS Attenuates Estradiol-Induced Endometrial Hyperplasia in Rats by Modulation of NF-κB and Nrf2/HO-1 Axes
Authors: Binmahfouz Lenah S. , Eid Basma G. , Bagher Amina M. , Shaik Rasheed A. , Binmahfouz Najlaa S. , Abdel-Naim Ashraf B.
Published: May 2022

Endometrial hyperplasia (EH) is the most common risk factor for endometrial malignancy in females. The pathogenesis of EH has been directly linked to uterine inflammation, which can result in abnormal cell division and decreased apoptosis. Piceatannol (PIC), a natural polyphenolic stilbene, is known to exert anti-inflammatory, antioxidant and anti-proliferative activities. The aim of the present study was to examine the potential preventive role of PIC in estradiol benzoate (EB)-induced EH in rats. A self-nanoemulsifying drug delivery system (SNEDDS) was prepared to improve the solubility of the PIC. Therefore, thirty female Wistar rats were divided into five groups: (1) control, (2) PIC SNEDDS (10 mg/kg), (3) EB (0.6 mg/kg), (4) EB + PIC SNEDDS (5 mg/kg) and (5) EB + PIC SNEDDS (10 mg/kg). The administration of PIC SNEDDS prevented EB-induced increases in uterine weights and histopathological changes. Additionally, it displayed pro-apoptotic and antioxidant activity in the endometrium. Immunohistochemical staining of uterine sections co-treated with PIC SNEDDS showed significantly decreased expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nuclear transcription factor-kappa B (NF-κB). This anti-inflammatory effect was further confirmed by a significant increase in Nrf2 and heme oxygenase-1 (HO-1) expression. These results indicate that SNEDDS nanoformulation of PIC possesses protective effects against experimentally induced EH.
Examination of Amorphous Calcium Carbonate on the Inflammatory and Muscle Damage Response in Experienced Resistance Trained Individuals
Authors: Hoffman Jay R. , Ben-Zeev Tavor , Zamir Amit , Levi Chagai , Ostfeld Ishay
Published: May 2022

The effect of 3 weeks of amorphous calcium carbonate (ACC) supplementation (2000 mg per day) was examined on the recovery response to resistance exercise. Thirty men were randomized into a supplement (ACC) or placebo (PL) group. Following supplementation, participants performed six sets of 10 repetitions in the bench press (BP) and incline BP exercises, using 80% of maximal strength. Participants returned 24 (T4) and 48 h (T5) later and performed six sets of the BP exercise. Significant decreases in the number of repetitions (p < 0.001), peak power (p < 0.001), and mean power (p = 0.009) were noted over time, but no significant interactions were observed (p > 0.05). Magnitude-based inference analysis (MBI) indicated that the change in repetitions was possibly beneficial for ACC at T4 and likely beneficial at T5. No significant interaction was noted for general soreness (p = 0.452), but a trend toward an interaction was observed in upper body soreness (p = 0.089). Confidence intervals for mean percent change scores indicated significant differences between the groups at T4 and T5, and MBI analysis indicated that ACC was very likely or likely to be beneficial for reducing soreness at those time points. In conclusion, ACC supplementation may have a potential beneficial effect in attenuating the decline in performance, which is possibly due to the carbonate component.
Bidirectional Associations between Parental Non-Responsive Feeding Practices and Child Eating Behaviors: A Systematic Review and Meta-Analysis of Longitudinal Prospective Studies
Authors: Wang Jian , Zhu Bingqian , Wu Ruxing , Chang Yan-Shing , Cao Yang , Zhu Daqiao
Published: May 2022

Background: Parental non-responsive feeding practices and child eating behaviors both play significant roles in childhood obesity. However, their longitudinal relationships are less clear. This systematic review aimed to examine their bidirectional associations. Methods: A systematic search of five databases was conducted from inception to February 2022. Data synthesis was performed using a semi-quantitative and quantitative approach. Results: A total of 14 studies with 15348 respondents were included. A total of 94 longitudinal effects from 14 studies of parental non-responsive feeding practices on child eating behaviors were investigated, and 19 statistically significant effects were discovered. Seventy-seven longitudinal effects from nine studies of child eating behaviors on parental feeding practices were examined, with fifteen being statistically significant. The pooled results of meta-analysis showed five statistically significant associations: parental restrictive feeding positively predicted child enjoyment of food (β = 0.044; 95% CI: 0.004, 0.085); use of food as a reward positively predicted child emotional eating (β = 0.09; 95% CI: 0.04, 0.15); child food responsiveness positively predicted restrictive feeding (β = 0.04; 95% CI: 0.02, 0.06); use food as a reward (β = 0.06; 95% CI: 0.03, 0.10). In addition, the pooled effects showed that child satiety responsiveness negatively predicted restrictive feeding (β = −0.05; 95% CI: −0.08, −0.01). Conclusions: The bidirectional relationships between parental non-responsive feeding practices and child eating behaviors are inconsistent and a few showed statistical significance. Theory-driven longitudinal studies using validated instruments and controlling for potential confounders are needed to unveil their relationships and provide evidence for obesity prevention interventions.
Effects of a Formula with scGOS/lcFOS (9:1) and Glycomacropeptide (GMP) Supplementation on the Gut Microbiota of Very Preterm Infants
Authors: Yu Xue , Xing Yan , Liu Hui , Chang Yanmei , You Yanxia , Dou Yuqi , Liu Bin , Wang Qi , Ma Defu , Chen Lijun , Tong Xiaomei
Published: May 2022

Microbial colonization of very preterm (VPT) infants is detrimentally affected by the complex interplay of physiological, dietary, medical, and environmental factors. The aim of this study was to evaluate the effects of an infant formula containing the specific prebiotic mixture of scGOS/lcFOS (9:1) and glycomacropeptide (GMP) on the composition and function of VPT infants’ gut microbiota. Metagenomic analysis was performed on the gut microbiota of VPT infants sampled at four time points: 24 h before the trial and 7, 14, and 28 days after the trial. Functional profiling was aggregated into gut and brain modules (GBMs) and gut metabolic modules (GMMs) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Enterococcus faecium, Escherichia coli, Klebsiella aerogenes, and Klebsiella pneumoniae were dominant species in both the test group and the control group. After the 4-week intervention, the abundance of Bifidobacterium in the test group was significantly increased. We found two GBMs (quinolinic acid synthesis and kynurenine degradation) and four GMMs (glutamine degradation, glyoxylate bypass, dissimilatory nitrate reduction, and preparatory phase of glycolysis) were significantly enriched in the test group, respectively. The results of this study suggested that formula enriched with scGOS/lcFOS (9:1) and GPM is beneficial to the intestinal microecology of VPT infants.
Modulation of Dyslipidemia Markers Apo B/Apo A and Triglycerides/HDL-Cholesterol Ratios by Low-Carbohydrate High-Fat Diet in a Rat Model of Metabolic Syndrome
Authors: Alnami Abrar , Bima Abdulhadi , Alamoudi Aliaa , Eldakhakhny Basmah , Sakr Hussein , Elsamanoudy Ayman
Published: May 2022

Metabolic syndrome (MetS) risks cardiovascular diseases due to its associated Dyslipidemia. It is proposed that a low-carbohydrate, high-fat (LCHF) diet positively ameliorates the MetS and reverses insulin resistance. Therefore, we aimed to investigate the protecting effect of the LCHF diet on MetS-associated Dyslipidemia in an experimental animal model. Forty male Sprague-Dawley rats were divided into four groups (10/group): the control group, dexamethasone-induced MetS (DEX) (250 µg/kg/day), LCHF-fed MetS group (DEX + LCHF), and High-Carbohydrate-Low-Fat-fed MetS group (DEX + HCLF). At the end of the four-week experiment, fasting glucose, insulin, lipid profile (LDL-C, HDL-C, Triglyceride), oxidized-LDL, and small dense-LDL using the ELISA technique were estimated. HOMA-IR, Apo B/Apo A1 ratio, and TG/HDL were calculated. Moreover, histological examination of the liver by H & E and Sudan III stain was carried out. In the DEX group, rats showed a significant (p < 0.05) increase in the HOMA-IR, atherogenic parameters, such as s-LDL, OX-LDL, Apo B/Apo A1 ratio, and TG/HDL. The LCHF diet significantly improved the parameters of Dyslipidemia (p < 0.05) by decreasing the Apo B/Apo A1 and TG/HDL-C ratios. Decreased steatosis in LCHF-fed rats compared to HCLF was also revealed. In conclusion, the LCHF diet ameliorates MetS-associated Dyslipidemia, as noted from biochemical results and histological examination.
Anthocyanins in Red Jasmine Rice (Oryza sativa L.) Extracts and Efficacy on Inhibition of Herpes Simplex Virus, Free Radicals and Cancer Cell
Authors: Suantai Boonpa , Jantakee Kanyaluck , Kaewkod Thida , Sangboonruang Sirikwan , Chitov Thararat , Tragoolpua Yingmanee
Published: May 2022

Rice is one of the most important food crops in many countries, with nutritional value and health benefits. In this study, the ethanolic and aqueous extracts of red jasmine rice from Chiang Mai, Thailand were examined for their anthocyanins and phenolic contents. The antioxidant and antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as well as anticancer activity, were investigated. The total anthocyanins content of 708.03 ± 11.56 mg Cy-3-glc equivalent/g extract, determined from the ethanolic extract, was higher than the aqueous extract. However, the aqueous extract showed the highest total phenolic compound of 81.91 ± 0.51 mg GAE/g extract. In addition, the ethanolic extract demonstrated higher antioxidant activity than aqueous extract using DPPH, ABTS, and FRAP assays by 28.91 ± 3.26 mg GAE/g extract, 189.45 ± 11.58 mg 24 TEAC/g extract, and 3292.46 ± 259.64 g FeSO4/g extract, respectively. In the antiviral assay, it was found that the ethanolic extract of red jasmine rice could inhibit HSV-1 more effectively than HSV-2 when treated before, during, and after the viral attachment on Vero cells, with 50% effective doses of 227.53 ± 2.41, 189.59 ± 7.76, and 192.62 ± 2.40 µg/mL, respectively. The extract also demonstrated the highest reduction of HSV-1 particles at 4 h after treatment and the inhibition of HSV-1 replication. The ethanolic extract exhibited a higher toxicity level than the aqueous extract, as well as the potential to induce DNA fragmentation by intrinsic and extrinsic apoptosis pathways on the Caco-2 cells. These findings suggest that red jasmine rice extract demonstrates nutritional value and biological activity on HSV, free radicals, and cancer cell inhibition.
Iron Metabolism following Twice a Day Endurance Exercise in Female Long-Distance Runners
Authors: Ishibashi Aya , Maeda Naho , Kojima Chihiro , Goto Kazushige
Published: May 2022

Iron deficiency anemia (IDA) and iron deficiency (ID) are frequently observed among endurance athletes. The iron regulatory hormone hepcidin may be involved in IDA and/or ID. Endurance athletes incorporate multiple training sessions, but the influence of repeated bouts of endurance exercise within the same day on iron metabolism remains unclear. Therefore, the purpose of the present study was to investigate the influence of twice a day endurance exercise on iron metabolism, including the hepcidin level, in female long-distance runners. Thirteen female long-distance runners participated in this study. They completed the twice-a-day endurance exercise in the morning and afternoon. Blood samples were collected four times in total: at 06:00 (P0), 14:00 (P8), 20:00 (P14), and 06:00 the next day (P24). In addition to the blood variables, nutritional intake was assessed throughout the exercise day. Serum hepcidin levels were significantly elevated (compared to P0) until the following morning (P24). Moreover, dietary analysis revealed that subjects consumed a low volume of carbohydrates (<6 g/kg body mass/day). In conclusion, twice a day endurance exercise resulted in significant elevation of serum hepcidin level 24 h after completion of the exercise in female long-distance runners. Therefore, athletes with a high risk of anemia should pay attention to training frequency and nutritional intake in order to maintain optimal iron metabolism.
Do Diet and Dietary Supplements Mitigate Clinical Outcomes in COVID-19?
Authors: Singh Bhavdeep , Eshaghian Eli , Chuang Judith , Covasa Mihai
Published: May 2022

The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authorities and citizens around the globe are still grappling with to this day. While public health measures, vaccine development, and new therapeutics have made great strides in understanding and managing the pandemic, there has been an increasing focus on the potential roles of diet and supplementation in disease prevention and adjuvant treatment. In the literature, the impact of nutrition on other respiratory illnesses, including the common cold, pneumonia, and influenza, has been widely demonstrated in both animal and human models. However, there is much less research on the impact related to COVID-19. The present study discusses the potential uses of diets, vitamins, and supplements, including the Mediterranean diet, glutathione, zinc, and traditional Chinese medicine, in the prevention of infection and severe illness. The evidence demonstrating the efficacy of diet supplementation on infection risk, disease duration, severity, and recovery is mixed and inconsistent. More clinical trials are necessary in order to clearly demonstrate the contribution of nutrition and to guide potential therapeutic protocols.
Angiodrastic Chemokines Production by Colonic Cancer Cell Lines
Authors: George Emmanouil , Andrew Moursellas , Maria Tzardi , Argyro Voumvouraki , Elias Kouroumalis
Published: May 2022

Purpose: To study the production of angiodrastic chemokines by colonic cancer cell lines. Methods: A pro-angiogenic factor (VEGF), two angiogenic chemokines (CXCL8, CXCL6), and one angiostatic (CXCL4) chemokine were measured by ELISA in the supernatants of the colon cancer cell lines HT-29 and Caco-2. Cells were cultured for 24 h in the presence of serum from cancer patients or healthy individuals. Results were analyzed by one-way ANOVA and the General Linear Model for repeated measures. Results: Colonic epithelial cells are potent producers of angiodrastic chemokines. HT-29 and Caco-2 cells produce all four chemokines under basal conditions and 24 h after incubation with human serum. The secretion response, however, was completely different. HT-29 cells produce more CXCL8 and VEGF irrespective of culture conditions, while Caco-2 cells seem unresponsive with respect to CXCL6 and CXCL4. Moreover, HT-29 cells produce more CXCL8 and VEGF when incubated with cancer serum, contrary to Caco-2 cells which produce more CXCL4 under the same conditions. Conclusions: The two colon cancer cell lines were producers of all chemokines studied, but their responses were not uniform under similar culture conditions. CXCL8 and VEGF are differently regulated compared to CXCL4 and CXCL6 in these two cell lines
Therapeutic Penetrating Keratoplasty in a Case of Corneal Perforation Caused by Colletotrichum gloeosporioides Infection
Authors: Imai Kazuki , Sumioka Takayoshi , Iwanishi Hiroki , Takada Yukihisa , Murata Shin’ichi , Iwamoto Ryuta , Okada Yuka , Saika Shizuya
Published: May 2022

Background: Corneal infection of Colletotrichum gloeosporioides is uncommon and usually limited to the anterior stroma. However, we observed a case of corneal stromal perforation caused by this fungus under a compromised condition. Case: A 73-year-old woman consulted us with a severe corneal ulceration. She was a tangerine orange farmer who suffered from rheumatoid arthritis for more than ten years. Before consultation with us, she received pterygium excision in her right eye. She then developed a corneal ulceration and received topical glucocorticoid therapy upon diagnosis of rheumatoid arthritis-related stromal ulcer in the eye. At the first consultation with us, a corneal ulceration was observed in the inferotemporal area of her right cornea. Biological examination detected a filamentous fungus, Colletotrichum gloeosporioides. Topical and systemic antifungal treatments were not significantly effective. Fourteen days after consultation, the lesion grew worse, leading to stromal perforation, which was treated by therapeutic penetrating keratoplasty using a preserved corneal button. Conclusions: Topical glucocorticoid could accelerate the growth of Colletotrichum gloeosporioides before diagnosis, even though the primary cause of corneal ulceration development might be rheumatoid arthritis.
Environmental Monitoring for Enteroviruses in Maputo, Mozambique—2018
Authors: Bero Diocreciano Matias , Nhassengo Sheila António , Sousa Ivanildo Pedro , de Sousa Silas Oliveira , Machado Raiana Scerni , Dias Amanda Meireles Nunes , de Sousa Ferreira Cristiane , Burlandy Fernanda Marcicano , de Deus Nilsa , da Silva Edson Elias
Published: May 2022

Due to the possibility of wild poliovirus importation from endemic regions and the high circulation of vaccine-derived poliovirus type 2 in the African region, Mozambique implemented a surveillance program to monitor the circulation of enteroviruses in the environment. From January to November 2018, a period that immediately preceded the cVDPV outbreak in Africa, 63 wastewater samples were collected from different areas in Maputo city. A total of 25 samples (39.7%) were positive based on cell culture isolation. Non-polio enteroviruses were found in 24 samples (24/25; 96%), whereas 1 Sabin-related poliovirus was isolated. Neither wild nor vaccine-derived poliovirus was detected. High circulation of EVB species was detected. Environmental surveillance in the One Health approach, if effectively applied as support to acute flaccid paralysis, can be a powerful aid to the public health system to monitor poliovirus besides non-polio enteroviruses in polio-free areas.
Mechanistic Insights on the In Vitro Antibacterial Activity and In Vivo Hepatoprotective Effects of Salvinia auriculata Aubl against Methotrexate-Induced Liver Injury
Authors: Attallah Nashwah G. M. , Mokhtar Fatma Alzahraa , Elekhnawy Engy , Heneidy Selim Z. , Ahmed Eman , Magdeldin Sameh , Negm Walaa A. , El-Kadem Aya H.
Published: May 2022

Methotrexate (MTX) is widely used in the treatment of numerous malignancies; however, its use is associated with marked hepatotoxicity. Herein, we assessed the possible hepatoprotective effects of Salvinia auriculata methanol extract (SAME) against MTX-induced hepatotoxicity and elucidated the possible fundamental mechanisms that mediated such protective effects for the first time. Forty mice were randomly allocated into five groups (eight/group). Control saline, MTX, and MTX groups were pre-treated with SAME 10, 20, and 30 mg/kg. The results revealed that MTX caused a considerable increase in blood transaminase and lactate dehydrogenase levels, oxidative stress, significant activation of the Nod-like receptor-3 (NLPR3)/caspase-1 inflammasome axis, and its downstream inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). MTX also down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Additionally, it increased the immunostaining of nuclear factor kappa-B (NF-κB) and downstream inflammatory mediators. Furthermore, the hepatic cellular apoptosis was dramatically up-regulated in the MTX group. On the contrary, prior treatment with SAME significantly improved biochemical, histopathological, immunohistochemical alterations caused by MTX in a dose-dependent manner. The antibacterial activity of SAME has also been investigated against Acinetobacter baumannii clinical isolates. LC-ESI-MS/MS contributed to the authentication of the studied plant and identified 24 active constituents that can be accountable for the SAME-exhibited effects. Thus, our findings reveal new evidence of the hepatoprotective and antibacterial properties of SAME that need further future investigation.
Brain Glucose Hypometabolism and Iron Accumulation in Different Brain Regions in Alzheimer’s and Parkinson’s Diseases
Authors: Rao Indira Y. , Hanson Leah R. , Johnson Julia C. , Rosenbloom Michael H. , Frey William H.
Published: May 2022

The aim of this study was to examine the relationship between the presence of glucose hypometabolism (GHM) and brain iron accumulation (BIA), two potential pathological mechanisms in neurodegenerative disease, in different regions of the brain in people with late-onset Alzheimer’s disease (AD) or Parkinson’s disease (PD). Studies that conducted fluorodeoxyglucose positron emission tomography (FDG-PET) to map GHM or quantitative susceptibility mapping—magnetic resonance imaging (QSM–MRI) to map BIA in the brains of patients with AD or PD were reviewed. Regions of the brain where GHM or BIA were reported in each disease were compared. In AD, both GHM and BIA were reported in the hippocampus, temporal, and parietal lobes. GHM alone was reported in the cingulate gyrus, precuneus and occipital lobe. BIA alone was reported in the caudate nucleus, putamen and globus pallidus. In PD, both GHM and BIA were reported in thalamus, globus pallidus, putamen, hippocampus, and temporal and frontal lobes. GHM alone was reported in cingulate gyrus, caudate nucleus, cerebellum, and parietal and occipital lobes. BIA alone was reported in the substantia nigra and red nucleus. GHM and BIA are observed independent of one another in various brain regions in both AD and PD. This suggests that GHM is not always necessary or sufficient to cause BIA and vice versa. Hypothesis-driven FDG-PET and QSM–MRI imaging studies, where both are conducted on individuals with AD or PD, are needed to confirm or disprove the observations presented here about the potential relationship or lack thereof between GHM and BIA in AD and PD.
Development of a Hospital Compounded, Taste-Masked, Temozolomide Oral Suspension and 5-Year Real-Life Experience in Treating Paediatric Patients
Authors: Annereau Maxime , Hinterlang Mélanie , Bienayme Hugues , Vassal Gilles , Pinon Antoine , Schmitt Mathieu , Denis Lucas , Lemarchand Caroline , Martin Laurent , Lemare François , Abbou Samuel , Bastid Jérémy , Tortolano Lionel
Published: May 2022

The development of oral pediatric forms by pharmaceutical companies is still insufficient. In fact, many drugs used in paediatric oncology, such as temozolomide, are not labeled and adapted for paediatric use. Temozolomide (TMZ) is an alkylating agent used as the standard of care for many adult and pediatric brain tumours, such as neuroblastoma, glioblastoma and medulloblastoma. The present study was carried out to propose a suitable and palatable formulation of the oral liquid preparation of TMZ. The suspension is composed of TMZ suspended in SyrSpend SF pH 4, as well as TMZ crystallization stabilizing agents and sweetening agents. To reach this formulation, several taste-masking agents were evaluated. Here, we describe the method of preparation of the formation as well as the monocentric population treated with the formulation over a 5–year period. A 20 mg/mL TMZ suspension was developed. TMZ suspension is stable for 6 weeks, stored between 2 and 8 degrees, protected from light, and compatible with nasogastric tubes. Thirty-eight patients participated in the palatability study and choose cola flavour, and 104 patients were treated in Gustave Roussy with the developed suspension; no unexpected event was reported. To conclude, we propose here a new TMZ liquid formulation which is stable for at least 6 weeks and well-tolerated with extensive feedback.
Identification of Potential RBPJ-Specific Inhibitors for Blocking Notch Signaling in Breast Cancer Using a Drug Repurposing Strategy
Authors: Rui Mengjie , Cai Min , Zhou Yu , Zhang Wen , Gao Lianglai , Mi Ke , Ji Wei , Wang Dan , Feng Chunlai
Published: May 2022

Notch signaling is a key parameter in regulating cell fate during tissue homeostasis, and an aberrant Notch pathway can result in mammary gland carcinoma and has been associated with poor breast cancer diagnosis. Although inhibiting Notch signaling would be advantageous in the treatment of breast cancer, the currently available Notch inhibitors have a variety of side effects and their clinical trials have been discontinued. Thus, in search of a more effective and safer Notch inhibitor, inhibiting recombinant signal binding protein for immunoglobin kappaJ region (RBPJ) specifically makes sense, as RBPJ forms a transcriptional complex that activates Notch signaling. From our established database of more than 10,527 compounds, a drug repurposing strategy-combined docking study and molecular dynamic simulation were used to identify novel RBPJ-specific inhibitors. The compounds with the best performance were examined using an in vitro cellular assay and an in vivo anticancer investigation. Finally, an FDA-approved antibiotic, fidaxomicin, was identified as a potential RBPJ inhibitor, and its ability to block RBPJ-dependent transcription and thereby inhibit breast cancer growth was experimentally verified. Our study demonstrated that fidaxomicin suppressed Notch signaling and may be repurposed for the treatment of breast cancer.
Bioassay-Guided Isolation of 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol from Oroxylum indicum and the Investigation of Its Molecular Mechanism Action of Apoptosis Induction
Authors: Singh Asem Robinson , Singh Salam Asbin , Singh Thangjam Davis , Singh Naorem Tarundas , Machathoibi Takhellambam Chanu , Singh Okram Mukherjee , Singh Lisam Shanjukumar
Published: May 2022

The leaf crude extract of Oroxylum indicum (L.) Kurz induces genomic DNA fragmentation, comet formation, and the inhibition of cell proliferation in the prostate cancer cell line PC3, as assessed by agarose gel electrophoresis, comet assay and MTT assay, respectively. The bioactive compound was purified through bioassay-guided fractionation using preparative HPLC and MTT assay. The light brown and water-soluble compound was characterized using 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR), and electrospray ionization (ESI) mass spectrometry. The compound was identified as a glycosylated hydroquinone derivative, 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl) tetrahy-dro-2H-pyran-3,4,5-triol (molecular formula, C13H18N2O8; molecular mass = 330). The identified phytocompound has not been reported earlier elsewhere. Therefore, the common name of the novel anticancer phytocompound isolated from Oroxylum indicum in this current study is oroxyquinone. The half-maximal inhibitory concentration (IC50) of oroxyquinone on PC3 cells was 58.9 µM (95% CI = 54.5 to 63.7 µM). Treatment of PC3 cells with oroxyquinone induced genomic DNA fragmentation and chromatin condensation, increased in the annexin-V positive cells, arrested the cell cycle at S phases, and inhibited the cell migration; as assessed by comet assay, DAPI staining, flow cytometry and a wound healing assay, respectively. On the investigation of the molecular mechanism of the induction of apoptosis, the results indicated that oroxyquinone induced caspase-3 and PARP independent apoptosis but through the p38 pathway and the localization of AIF into the nucleus. The present study identifies a novel anticancer molecule and provides scientific evidence supporting the therapeutic potency of Oroxylum indicum for ethnomedicinal uses.
Induced Pluripotent Stem Cell-Based Drug Screening by Use of Artificial Intelligence
Authors: Kusumoto Dai , Yuasa Shinsuke , Fukuda Keiichi
Published: May 2022

Induced pluripotent stem cells (iPSCs) are terminally differentiated somatic cells that differentiate into various cell types. iPSCs are expected to be used for disease modeling and for developing novel treatments because differentiated cells from iPSCs can recapitulate the cellular pathology of patients with genetic mutations. However, a barrier to using iPSCs for comprehensive drug screening is the difficulty of evaluating their pathophysiology. Recently, the accuracy of image analysis has dramatically improved with the development of artificial intelligence (AI) technology. In the field of cell biology, it has become possible to estimate cell types and states by examining cellular morphology obtained from simple microscopic images. AI can evaluate disease-specific phenotypes of iPS-derived cells from label-free microscopic images; thus, AI can be utilized for disease-specific drug screening using iPSCs. In addition to image analysis, various AI-based methods can be applied to drug development, including phenotype prediction by analyzing genomic data and virtual screening by analyzing structural formulas and protein–protein interactions of compounds. In the future, combining AI methods may rapidly accelerate drug discovery using iPSCs. In this review, we explain the details of AI technology and the application of AI for iPSC-based drug screening.