bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition, Cognition, and Social Emotion among Preschoolers in Poor, Rural Areas of South Central China: Status and Correlates
Authors: Chen Kevin , Liu Chengfang , Liu Xinghua , Wang Zimeiyi , Luo Renfu , Li Shaoping , Yu Yanying , Alderman Harold
Published: April 2021

Existing empirical evidence suggests that the prevalence of undernutrition in remote and poor, rural areas is still high among Chinese children. While evidence reveals that undernutrition may detrimentally affect child development, studies focusing on rural Chinese preschoolers are sparse. Using the baseline survey of a preschool’s free nutritious lunch pilot program, this study examined the relationship between child undernutrition and developmental outcomes among a preschool-aged sample in poor, rural areas of China. We conducted the baseline survey in Hunan province in south central China in September 2018. A total of 1293 preschoolers living in two (then) nationally designated poverty counties in rural Hunan served as our study sample. Children’s nutritional statuses were measured using height-for-age z-score, weight-for-age z-score, and anemia, while their cognitive and socio-emotional skills were assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and Strengths and Difficulties Questionnaire (SDQ), respectively. We find that 33% of sample preschoolers were anemic, whereas the incidences of stunting and wasting were 11% and 2%, respectively. About 54% of the sample children had delay in at least one of the developmental domains measured in this study. Our findings provide suggestive evidence supporting that children from certain backgrounds tend to experience worse nutritional and developmental outcomes than their counterparts. After controlling for socioeconomic status, we observed that both anemia and stunting were negatively associated with children’s cognitive performance; however, they were not associated with socio-emotional performance. As such, this study suggests that free lunch programs have the potential to change children’s developmental trajectory in preschool. We believe that our results will contribute to the debate surrounding whether the nutritious lunch program in China should be expanded to the preschool education level.
Diet–Cognition Associations Differ in Mild Cognitive Impairment Subtypes
Authors: Huang Qiumin , Jia Xiaofang , Zhang Jiguo , Huang Feifei , Wang Huijun , Zhang Bing , Wang Liusen , Jiang Hongru , Wang Zhihong
Published: April 2021

Cognitive function is not generally associated with diet, and there is debate over that association. Moreover, little is known about such associations with the specific cognitive domains and subtypes of mild cognitive impairment (MCI). We analyzed data of 4309 Chinese adults aged 55 and over from the Community-based Cohort Study on Nervous System Diseases from 2018–2019. Dietary habits were assessed at inclusion using a validated semi-quantitative food frequency questionnaire. Cognitive function of the participants was measured by using the Montreal Cognitive Assessment. Analyses were performed using multiple logistic regression and quantile regression with adjustment for socio-demographic, lifestyle, and health-related factors. Compared with normal cognition participants, those with a worse cognition state were characterized as being an older age and lower economic level. After adjustment for potential factors, participants with higher consumption of rice, legumes, fresh vegetables, fresh fruit, pork, poultry, fish, and nuts tended to have higher scores of global cognitive function and domains, and to have lower odds of MCI, while those with higher consumption levels of wheat and eggs had worse cognition, compared with the corresponding bottom consumption level of each food. Participants with a medium consumption level of beef or mutton had 57% (OR: 1.57, 95%CI: 1.07–2.32) higher odds of aMCI-SD, whereas they had 50% (OR: 0.50, 95%CI: 0.34–0.73) lower odds of naMCI-MD. Similarly, the highest consumption level of dairy was positively associated with the odds of aMCI-SD (OR:1.51, 95%CI:1.00–2.29), but inversely linked to the odds of naMCI-SD (OR: 0.60, 95%CI: 0.38–0.93) and naMCI-MD (OR: 0.49, 95%CI: 0.29–0.82). Most diet global cognitive benefits were observed to be associated with the preexisting higher consumption of rice, legumes, fresh vegetables, fresh fruit, meat, and nuts. In addition, the heterogeneity of associations between the consumption of certain foods and MCI subtypes was observed among Chinese adults aged over 55 years. These cross-sectional observations require validation in prospective studies.
Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss, Glucose Metabolism, Insulin Kinetics and β-Cell Function in Morbidly Obese Individuals
Authors: Tricò Domenico , Moriconi Diego , Berta Rossana , Baldi Simona , Quinones-Galvan Alfredo , Guiducci Letizia , Taddei Stefano , Mari Andrea , Nannipieri Monica
Published: April 2021

Low-calorie Mediterranean-style or low-carbohydrate dietary regimens are widely used nutritional strategies against obesity and associated metabolic diseases, including type 2 diabetes. The aim of this study was to compare the effectiveness of a balanced Mediterranean diet with a low-carbohydrate diet on weight loss and glucose homeostasis in morbidly obese individuals at high risk to develop diabetes. Insulin secretion, insulin clearance, and different β-cell function components were estimated by modeling plasma glucose, insulin and C-peptide profiles during 75-g oral glucose tolerance tests (OGTTs) performed at baseline and after 4 weeks of each dietary intervention. The average weight loss was 5%, being 58% greater in the low-carbohydrate-group than Mediterranean-group. Fasting plasma glucose and glucose tolerance were not affected by the diets. The two dietary regimens proved similarly effective in improving insulin resistance and fasting hyperinsulinemia, while enhancing endogenous insulin clearance and β-cell glucose sensitivity. In summary, we demonstrated that a low-carbohydrate diet is a successful short-term approach for weight loss in morbidly obese patients and a feasible alternative to the Mediterranean diet for its glucometabolic benefits, including improvements in insulin resistance, insulin clearance and β-cell function. Further studies are needed to compare the long-term efficacy and safety of the two diets.
Interventions to Promote Healthy Meals in Full-Service Restaurants and Canteens: A Systematic Review and Meta-Analysis
Authors: Mandracchia Floriana , Tarro Lucia , Llauradó Elisabet , Valls Rosa Maria , Solà Rosa
Published: April 2021

Out-of-home eating is increasing, but evidence about its healthiness is limited. The present systematic review and meta-analysis aimed to elucidate the effectiveness of full-service restaurant and canteen-based interventions in increasing the dietary intake, food availability, and food purchase of healthy meals. Studies from 2000–2020 were searched in Medline, Scopus, and Cochrane Library using the PRISMA checklist. A total of 35 randomized controlled trials (RCTs) and 6 non-RCTs were included in the systematic review and analyzed by outcome, intervention strategies, and settings (school, community, workplace). The meta-analysis included 16 RCTs (excluding non-RCTs for higher quality). For dietary intake, the included RCTs increased healthy foods (+0.20 servings/day; 0.12 to 0.29; p < 0.001) and decreased fat intake (−9.90 g/day; −12.61 to −7.19; p < 0.001), favoring the intervention group. For food availability, intervention schools reduced the risk of offering unhealthy menu items by 47% (RR 0.53; 0.34 to 0.85; p = 0.008). For food purchases, a systematic review showed that interventions could be partially effective in improving healthy foods. Lastly, restaurant- and canteen-based interventions improved the dietary intake of healthy foods, reduced fat intake, and increased the availability of healthy menus, mainly in schools. Higher-quality RCTs are needed to strengthen the results. Moreover, from our results, intervention strategy recommendations are provided.
Food Addiction and Lifestyle Habits among University Students
Authors: Romero-Blanco Cristina , Hernández-Martínez Antonio , Parra-Fernández María Laura , Onieva-Zafra María Dolores , Prado-Laguna María del Carmen , Rodríguez-Almagro Julián
Published: April 2021

The prevalence of overweight and obesity is increasing in our society, with a complex, multifactorial origin, and associated with greater morbidity and mortality in the population. Food addiction (FA) is a common disorder in overweight/obese people, which appears to be increasingly common in young people. This study analyzed food addiction in a group of young university students and to examine its association with body composition, quality of sleep, adherence to the Mediterranean diet, physical activity/sedentary habits, tobacco or alcohol consumption, and health status. A total of 536 undergraduate nursing students participated in a questionnaire that included the Yale Food Addiction Scale (YFAS 2.0). Up to 6.4% of the students presented FA. Statistically significant associations were observed in the variables for sleep quality odds ratio (OR) 4.8 (95% confidence interval (CI): 1.66–13.87), anxiety/depression OR 8.71 (95% CI: 3.93–19.27), body mass index (BMI) OR 8.32 (95% CI: 3.81–18.15) and sedentary lifestyle OR 2.33 (95% CI: 1.09–5.01). A predictive model was developed after binary logistic regression (area under the ROC curve 0.84 (95% CI: 0.77–0.91). Students with FA presented higher BMI values, worse sleep quality, anxiety or depression problems, and more time spent in sedentary behaviors.
Managing Obesity in Lockdown: Survey of Health Behaviors and Telemedicine
Authors: Minsky Noga C. , Pachter Dafna , Zacay Galia , Chishlevitz Naama , Ben-Hamo Miriam , Weiner Dana , Segal-Lieberman Gabriella
Published: April 2021

Since the outbreak of COVID-19, billions of people have gone into lockdown, facing pandemic related challenges that engender weight gain, especially in the obese. We report the results of an online survey, conducted during Israel’s first quarantine, of 279 adults treated in hospital-based obesity clinics with counseling, medications, surgery, endoscopic procedures, or any combination of these for weight loss. In this study, we assessed the association between changes in dietary and lifestyle habits and body weight, and the benefits of receiving weight management care remotely through telemedicine during lockdown. Compared to patients not receiving obesity care via telemedicine, patients receiving this care were more likely to lose weight (OR, 2.79; p = 0.042) and also to increase participation in exercise (OR, 2.4; p = 0.022). While 40% of respondents reported consuming more sweet or salty processed snacks and 33% reported less vegetables and fruits, 65% reported more homemade foods. At the same time, 40% of respondents reported a reduction in exercise and 52% reported a decline in mood. Alterations in these eating patterns, as well as in exercise habits and mood, were significantly associated with weight changes. This study highlights that lockdown affects health behaviors associated with weight change, and advocates for the use of telemedicine to provide ongoing obesity care during future quarantines in order to promote weight loss and prevent weight gain.
Analysis of the Effects of Nutrient Intake and Dietary Habits on Depression in Korean Adults
Authors: Yun Hyeonseo , Kim Dong-Wook , Lee Eun-Joo , Jung Jinmyung , Yoo Sunyong
Published: April 2021

While several studies have explored nutrient intake and dietary habits associated with depression, few studies have reflected recent trends and demographic factors. Therefore, we examined how nutrient intake and eating habits are associated with depression, according to gender and age. We performed simple and multiple regressions using nationally representative samples of 10,106 subjects from the Korea National Health and Nutrition Examination Survey. The results indicated that cholesterol, dietary fiber, sodium, frequency of breakfast, lunch, dinner, and eating out were significantly associated with depression (p-value < 0.05). Moreover, depression was associated with nutrient intake and dietary habits by gender and age group: sugar, breakfast, lunch, and eating out frequency in the young women’s group; sodium and lunch frequency among middle-age men; dietary fibers, breakfast, and eating out frequency among middle-age women; energy, moisture, carbohydrate, lunch, and dinner frequency in late middle-age men; breakfast and lunch frequency among late middle-age women; vitamin A, carotene, lunch, and eating out frequency among older age men; and fat, saturated fatty acids, omega-3 fatty acid, omega-6 fatty acid, and eating out frequency among the older age women’s group (p-value < 0.05). This study can be used to establish dietary strategies for depression prevention, considering gender and age.
Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers
Authors: Norwitz Nicholas G. , Saif Nabeel , Ariza Ingrid Estrada , Isaacson Richard S.
Published: April 2021

The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction.
Global Trends (1961–2017) in Human Dietary Potassium Supplies
Authors: Kumssa Diriba B. , Joy Edward J. M. , Broadley Martin R.
Published: April 2021

Background: Potassium (K) is an essential mineral and major intracellular electrolyte involved in the regulation of blood pressure, muscle contraction and nerve transmission in humans. Major dietary sources of K include fruits and vegetables, starchy roots and tubers, and whole grains. The aim of this study was to assess and report: (i) the sufficiency of K in national food systems globally, (ii) to quantify the contribution from food groups, and (iii) to explore spatial and temporal trends in the period of 1961–2017. Methods: Food supply and demography (1961–2017), K composition and K requirement data were combined to estimate per capita human dietary supplies of potassium (DSK), adequate intake of K (AIK) and K sufficiency ratio (KSR) at national, regional, continental and global levels. Results and Discussion: Globally, the mean ± SD. DSK (mg capita−1 d−1) increased from 2984 ± 915 in 1961 to 3796 ± 1161 in 2017. There was a wide range in DSK between geographical regions and across years, with particularly large increases in east Asia, where DSK increased from <3000 to >5000 mg capita−1 day−1. Roots and tubers contributed the largest dietary source of K, providing up to 80% of DSK in most regions. At the global level, throughout the 57-year period, the population-weighted KSR was <1 based on the 2006 Institute of Medicine AIK recommendation, while it was >1 based on the 2019 National Academies of Science and the 2016 European Union AIK recommendation. While KSR ≥ 1 shows sufficiency of DSK, KSR < 1 does not indicate K deficiency risk. Conclusion: Due to the absence of a Recommended Daily Allowance (RDA) for K, this study used the ratio of DSK:AIK (i.e., KSR) to assess dietary K sufficiency. Estimates of dietary K sufficiency are, therefore, highly sensitive to the AIK reference value used and this varied greatly based on different institutions and years. To quantify the risk of dietary K deficiency, bridging the data gap to establish an RDA for K should be a global research priority.
Influence of Implant-Abutment Contact Surfaces and Prosthetic Screw Tightening on the Stress Concentration, Fatigue Life and Microgap Formation: A Finite Element Analysis
Authors: Tribst João Paulo Mendes , Dal Piva Amanda Maria de Oliveira , da Silva-Concílio Laís Regiane , Ausiello Pietro , Kalman Les
Published: April 2021

The purpose of this in silico study was to investigate the effect of abutment screw torque and implant-abutment contact surfaces on the stress generation, microgap formation and simulated fatigue life of an external hexagon connection under oblique loading. Three-dimensional numerical models of the external hexagon implant were modeled containing two different implant-abutment contact surfaces (with and without contacting the hexagon axial walls) as well as using screw torques of 20 Ncm or 30 Ncm. Following the ISO 14801, an oblique load of 100 N was applied to the prosthesis. The von Mises stress, microgap formation, safety factor and fatigue life were obtained. The stresses in the abutment screw and implant were minimally influenced by the screw torque. However, this minimal stress in the screw with a 30 Ncm torque reduced the calculated fatigue life in comparison with 20 Ncm when the external hexagon axial walls were not in contact at the implant-abutment interface. The safety factor for the implant was higher when using minimal surfaces at the abutment-interfaces; however, it compromised the screw safety factor increasing its failure probability. The higher the screw torque, the lower was the microgap formation at the implant-abutment interface. However, the calculated residual stress is proportional to the applied torque, reducing the fatigue life in the screw. This effect can be attenuated using an implant-abutment system with more contacting surfaces.
Thymoquinone, as a Novel Therapeutic Candidate of Cancers
Authors: Almajali Belal , Al-Jamal Hamid Ali Nagi , Taib Wan Rohani Wan , Ismail Imilia , Johan Muhammad Farid , Doolaanea Abd Almonem , Ibrahim Wisam Nabeel
Published: April 2021

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.
In Vitro Activity of a Novel Siderophore-Cephalosporin LCB10-0200 (GT-1), and LCB10-0200/Avibactam, against Carbapenem-Resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa Strains at a Tertiary Hospital in Korea
Authors: Nguyen Le , Park Chul , Pinto Naina , Lee Hyunsook , Seo Hyun , Vu Thao , Mai Hung , Pham An , Jang Eris , Cho Young , Goglin Karrie , Nguyen Kevin , White Richard , D’Souza Roshan , Fouts Derrick , Yong Dongeun
Published: April 2021

The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC- producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP- and NDM- producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.
The Influence of Plant Isoflavones Daidzein and Equol on Female Reproductive Processes
Authors: Sirotkin Alexander V. , Alwasel Saleh Hamad , Harrath Abdel Halim
Published: April 2021

In this review, we explore the current literature on the influence of the plant isoflavone daidzein and its metabolite equol on animal and human physiological processes, with an emphasis on female reproduction including ovarian functions (the ovarian cycle; follicullo- and oogenesis), fundamental ovarian-cell functions (viability, proliferation, and apoptosis), the pituitary and ovarian endocrine regulators of these functions, and the possible intracellular mechanisms of daidzein action. Furthermore, we discuss the applicability of daidzein for the control of animal and human female reproductive processes, and how to make this application more efficient. The existing literature demonstrates the influence of daidzein and its metabolite equol on various nonreproductive and reproductive processes and their disorders. Daidzein and equol can both up- and downregulate the ovarian reception of gonadotropins, healthy and cancerous ovarian-cell proliferation, apoptosis, viability, ovarian growth, follicullo- and oogenesis, and follicular atresia. These effects could be mediated by daidzein and equol on hormone production and reception, reactive oxygen species, and intracellular regulators of proliferation and apoptosis. Both the stimulatory and the inhibitory effects of daidzein and equol could be useful for reproductive stimulation, the prevention and mitigation of cancer development, and the adverse effects of environmental stressors in reproductive biology and medicine.
The Comparison of In Vitro Photosensitizing Efficacy of Curcumin-Loaded Liposomes Following Photodynamic Therapy on Melanoma MUG-Mel2, Squamous Cell Carcinoma SCC-25, and Normal Keratinocyte HaCaT Cells
Authors: Woźniak Marta , Nowak Martyna , Lazebna Anastasiia , Więcek Kamil , Jabłońska Izabella , Szpadel Krzysztof , Grzeszczak Aleksandra , Gubernator Jerzy , Ziółkowski Piotr
Published: April 2021

The research focused on the investigation of curcumin encapsulated in hydrogenated soy phosphatidylcholine liposomes and its increased photoactive properties in photodynamic therapy (PDT). The goal of this study was two-fold: to emphasize the role of a natural photoactive plant-based derivative in the liposomal formulation as an easily bioavailable, alternative photosensitizer (PS) for the use in PDT of skin malignancies. Furthermore, the goal includes to prove the decreased cytotoxicity of phototoxic agents loaded in liposomes toward normal skin cells. Research was conducted on melanoma (MugMel2), squamous cell carcinoma (SCC-25), and normal human keratinocytes (HaCaT) cell lines. The assessment of viability with MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) evaluated cell death after exposure to blue light irradiation after 4 h of pre-incubation with free and encapsulated curcumin. Additionally, the wound healing assay, flow cytometry, and immunocytochemistry to detect apoptosis were performed. The malignant cells revealed increased phototoxicity after the therapy in comparison to normal cells. Moreover, liposome curcumin-based photodynamic therapy showed an increased ratio of apoptotic and necrotic cells. The study also demonstrated that nanocurcumin significantly decreased malignant cell motility following PDT treatment. Acquired results suggest that liposomal formulation of a poor soluble natural compound may improve photosensitizing properties of curcumin-mediated PDT treatment in skin cancers and reduce toxicity in normal keratinocytes.
Characterization of Subtype Selective Cannabinoid CB2 Receptor Agonists as Potential Anti-Inflammatory Agents
Authors: Tang Yaliang , Wolk Barbara , Nolan Ryan , Scott Caitlin E. , Kendall Debra A.
Published: April 2021

Activation of the CB2 receptor has been shown to have anti-inflammatory and antinociceptive effects without causing psychoactive effects. Previously, we reported that the compound ethyl 2(2-(N-(2,3-dimethylphenyl) phenylsulfonamido)acetamido)benzoate (ABK5) is a CB2 subtype selective agonist with anti-inflammatory and antinociceptive effects. In the present study, we tested four ABK5 derivatives, ABK5-1, ABK5-2, ABK5-5, and ABK5-6, to analyze the structure of ABK5 to obtain CB2-selective agonists with higher affinity and efficacy. Affinity, subtype selectivity, and G-protein coupling were determined by radioligand binding assays. Selected compounds were then subjected to evaluation of anti-inflammatory effects using two different cell lines, Jurkat (ABK5-1 and 5-2) and BV-2 cells (ABK5-1), which are models of T cells and microglia, respectively. ABK5-1, ABK5-2, and ABK5-6 had comparable CB2 binding affinity with ABK5 (and stimulated G-protein coupling), while only ABK5-1 and ABK5-2 maintained CB2-subtype selectivity. ABK5-5 did not bind CB2 in the detectable range. RT-PCR and ELISA analysis showed that the two compounds also inhibit IL-2 and TNF-α production, and they were more efficacious than ABK5 in inhibiting TNF-α production. CXCL-12 mediated chemotaxis was also evaluated by the transwell migration assay, and both ABK5-1 and ABK5-2 inhibited chemotaxis with a stronger effect observed in ABK5-1. In the microglia cell line BV-2, ABK5-1 inhibited IL-1β and IL-6 production, which suggests this compound has anti-inflammatory effects through targeting multiple immune cells, and may be a candidate for treatment of inflammation.
Dexamethasone-Loaded Bioactive Coatings on Medical Grade Stainless Steel Promote Osteointegration
Authors: Rožanc Jan , Žižek Marko , Milojević Marko , Maver Uroš , Finšgar Matjaž
Published: April 2021

In this study, a multilayer bioactive coating based on carboxymethyl cellulose (CMC) and dexamethasone (DEX) was prepared on medical-grade stainless steel (AISI 316LVM). Its aim was the controlled drug delivery of the incorporated anti‑inflammatory drug, which at the same time promotes osteogenic differentiation of mesenchymal stem cells. Due to DEX’s limited solubility in physiological fluids, which limits the loading capacity of coatings, it was further combined with β-cyclodextrin to increase its concentration in the bioactive coating. Controlled release of DEX from the multilayer coating was achieved in four steps: a “burst”, i.e., very fast, release step (in an immersion interval of 0–10 min), a fast release step (10–30 min), a slow-release step (60–360 min), and a plateau step (360–4320 min), following a zero-order release or Higuchi model release mechanism. Successful layer-by-layer coating formation was confirmed using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). It was shown that the application of the coating significantly increases the hydrophilic character of AISI 316LVM, and also significantly increases the surface roughness, which is known to promote cell growth. In addition, electrochemical measurements demonstrated that the coating application does not increase the susceptibility of medical-grade stainless steel to corrosion. In vitro cell testing using all cell types with which such coatings come into contact in the body (osteoblasts, chondrocytes, and mesenchymal stem cells (MSCs)) showed very good biocompatibility towards all of the mentioned cells. It further confirmed that the coatings promoted MSCs osteogenic differentiation, which is the desired mode of action for orthopedic implants.
Oncogenic and Tumor Suppressive Components of the Cell Cycle in Breast Cancer Progression and Prognosis
Authors: Kashyap Dharambir , Garg Vivek Kumar , Sandberg Elise N. , Goel Neelam , Bishayee Anupam
Published: April 2021

Cancer, a disease of inappropriate cell proliferation, is strongly interconnected with the cell cycle. All cancers consist of an abnormal accumulation of neoplastic cells, which are propagated toward uncontrolled cell division and proliferation in response to mitogenic signals. Mitogenic stimuli include genetic and epigenetic changes in cell cycle regulatory genes and other genes which regulate the cell cycle. This suggests that multiple, distinct pathways of genetic alterations lead to cancer development. Products of both oncogenes (including cyclin-dependent kinase (CDKs) and cyclins) and tumor suppressor genes (including cyclin-dependent kinase inhibitors) regulate cell cycle machinery and promote or suppress cell cycle progression, respectively. The identification of cyclins and CDKs help to explain and understand the molecular mechanisms of cell cycle machinery. During breast cancer tumorigenesis, cyclins A, B, C, D1, and E; cyclin-dependent kinase (CDKs); and CDK-inhibitor proteins p16, p21, p27, and p53 are known to play significant roles in cell cycle control and are tightly regulated in normal breast epithelial cells. Following mitogenic stimuli, these components are deregulated, which promotes neoplastic transformation of breast epithelial cells. Multiple studies implicate the roles of both types of components—oncogenic CDKs and cyclins, along with tumor-suppressing cyclin-dependent inhibitors—in breast cancer initiation and progression. Numerous clinical studies have confirmed that there is a prognostic significance for screening for these described components, regarding patient outcomes and their responses to therapy. The aim of this review article is to summarize the roles of oncogenic and tumor-suppressive components of the cell cycle in breast cancer progression and prognosis.
Quantification of Teicoplanin Using the HPLC-UV Method for Clinical Applications in Critically Ill Patients in Korea
Authors: Lee Jaeok , Chung Eun-Kyoung , Kang Sung-Wook , Lee Hwa-Jeong , Rhie Sandy-Jeong
Published: April 2021

A high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method has been used to quantify teicoplanin concentrations in human plasma. However, the limited analytical accuracy of previously bioanalytical methods for teicoplanin has given rise to uncertainty due to the use of an external standard. In this study, an internal standard (IS), polymyxin B, was applied to devise a precise, accurate, and feasible HPLC-UV method. The deproteinized plasma sample containing teicoplanin and an IS of acetonitrile was chromatographed on a C18 column with an acidic mobile phase consisting of NaH2PO4 buffer and acetonitrile (78:22, v/v) by isocratic elution and detection at 220 nm. The linearity was in the range 7.8–500 mg/L calculated by the ratio of the teicoplanin signal to the IS signal. This analytical method, validated by FDA guidelines with ICH Q2 (R1), was successfully applied to analyze the plasma samples of patients in the intensive care unit for treating serious resistant bacterial infectious diseases, such as those by methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The methods suggested the potential for use in routine clinical practice for therapeutic drug monitoring of teicoplanin, providing both improved accuracy and a wide range of linearity from lower than steady-state trough concentrations (10 mg/L) to much higher concentrations.
Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid
Authors: Gao Xiuqing , Wu Lei , Tsai Robert Y. L. , Ma Jing , Liu Xiaohua , Chow Diana S.-L. , Liang Dong , Xie Huan
Published: April 2021

Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.
Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing
Authors: Reeves Micaela A. , Royal Joshua M. , Morris David A. , Jurkiewicz Jessica M. , Matoba Nobuyuki , Hamorsky Krystal T.
Published: April 2021

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit, modified with a C-terminal KDEL endoplasmic reticulum retention motif. EPT has therapeutic potential for ulcerative colitis treatment. Previously, orally administered EPT demonstrated colon epithelial repair activity in dextran sodium sulfate (DSS)-induced acute and chronic colitis in mice. However, the oral dosing requires cumbersome pretreatment with sodium bicarbonate to conserve the acid-labile drug substance while transit through the stomach, hampering its facile application in chronic disease treatment. Here, we developed a solid oral formulation of EPT that circumvents degradation in gastric acid. EPT was spray-dried and packed into enteric-coated capsules to allow for pH-dependent release in the colon. A GM1-capture KDEL-detection ELISA and size-exclusion HPLC indicated that EPT powder maintains activity and structural stability for up to 9 months. Capsule disintegration tests showed that EPT remained encapsulated at pH 1 but was released over 180 min at pH 6.8, the approximate pH of the proximal colon. An acute DSS colitis study confirmed the therapeutic efficacy of encapsulated EPT in C57BL/6 mice upon oral administration without gastric acid neutralization pretreatment compared to vehicle-treated mice (p < 0.05). These results provide a foundation for an enteric-coated oral formulation of spray-dried EPT.
The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa
Authors: Gbian Douweh Leyla , Omri Abdelwahab
Published: April 2021

The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against P. aeruginosa isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on P. aeruginosa biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 ± 33.74 nm for gentamicin and 3086.35 ± 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 ± 1.54% and 51.58 ± 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4–32 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients.
In-Depth Comparison of Dry Particle Coating Processes Used in DPI Particle Engineering
Authors: Bungert Nicholas , Kobler Mirjam , Scherließ Regina
Published: April 2021

High-shear mixer coatings as well as mechanofusion processes are used in the particle-engineering of dry powder inhalation carrier systems. The aim of coating the carrier particle is usually to decrease carrier–drug adhesion. This study comprises the in-depth comparison of two established dry particle coating options. Both processes were conducted with and without a model additive (magnesium stearate). In doing so, changes in the behaviour of the processed particles can be traced back to either the process or the additive. It can be stated that the coarse model carrier showed no significant changes when processed without additives. By coating the particles with magnesium stearate, the surface energy decreased significantly. This leads to a significant enhancement of the aerodynamic performance of the respective carrier-based blends. Comparing the engineered carriers with each other, the high-shear mixer coating shows significant benefits, namely, lower drug–carrier adhesion and the higher efficiency of the coating process.
Sesame Oil-Based Nanostructured Lipid Carriers of Nicergoline, Intranasal Delivery System for Brain Targeting of Synergistic Cerebrovascular Protection
Authors: Abourehab Mohammed A. S. , Khames Ahmed , Genedy Samar , Mostafa Shahin , Khaleel Mohammad A. , Omar Mahmoud M. , El Sisi Amani M.
Published: April 2021

Nicergoline (NIC) is a semisynthetic ergot alkaloid derivative applied for treatment of dementia and other cerebrovascular disorders. The efficacy of sesame oil to slow and reverse the symptoms of neurodegenerative cognitive disorders has been proven. This work aimed to formulate and optimize sesame oil-based NIC-nanostructured lipid carriers (NIC–NLCs) for intranasal (IN) delivery with expected synergistic and augmented neuroprotective properties. The NIC–NLC were prepared using sesame oil as a liquid lipid. A three-level, three-factor Box–Behnken design was applied to statistically optimize the effect of sesame oil (%) of the total lipid, surfactant concentration, and sonication time on particle size, zeta potential, and entrapment efficacy as responses. Solid-state characterization, release profile, and ex vivo nasal permeation in comparison to NIC solution (NIC–SOL) was studied. In vivo bioavailability from optimized NIC–NLC and NIC–SOL following IN and IV administration was evaluated and compared. The optimized NIC–NLC formula showed an average particle size of 111.18 nm, zeta potential of −15.4 mV, 95.11% entrapment efficacy (%), and 4.6% loading capacity. The NIC–NLC formula showed a biphasic, extended-release profile (72% after 48 h). Permeation of the NIC–NLC formula showed a 2.3 enhancement ratio. Bioavailability studies showed a 1.67 and 4.57 fold increase in plasma and brain following IN administration. The results also indicated efficient direct nose-to-brain targeting properties with the brain-targeting efficiency (BTE%) and direct transport percentage (DTP%) of 187.3% and 56.6%, respectively, after IN administration. Thus, sesame oil-based NIC–NLC can be considered as a promising IN delivery system for direct and efficient brain targeting with improved bioavailability and expected augmented neuroprotective action for the treatment of dementia.
Evaluation of Performance Enhancement of Optical Multi-Level Modulation Based on Direct Modulation of Optically Injection-Locked Semiconductor Lasers
Authors: Jeong Hyo-Sang , Cho Jun-Hyung , Sung Hyuk-Kee
Published: April 2021

The performance of optical M-level (multi-level) amplitude shift keying (ASK) modulation is improved by directly using modulated optically injection-locked (OIL) semiconductor lasers. The direct modulation performance of free-running and OIL semiconductor lasers is evaluated and compared theoretically based on coupled-rate equation. We have found that OIL semiconductor lasers can significantly improve the modulation performance in terms of the signal eye opening and Q-factor. Additionally, we found that the Q-factor increases even more in the negative frequency detuning range due to its dependence on the locking parameters.
Development of a Subpath Extrusion Tip and Die for Peripheral Inserted Central Catheter Shaft with Multi Lumen
Authors: Lee Han Chang , Jeong Jinhyuk , Jo Seunggi , Choi Dong Yun , Kim Gyu Man , Kim Woojin
Published: April 2021

The tip and die for manufacturing multi-lumen catheter tubes should be designed considering the flow velocity of the molten polymer and the deformation of the final extruded tube. In this study, to manufacture non-circular double-lumen tubes for peripherally inserted central catheters (PICCs), three types of tip and die structures are proposed. The velocity field and swelling effect when the circular tip and die (CTD) are applied, which is the commonly used tip and die structure, are analyzed through numerical calculation. To resolve the wall and rib thickness and ovality issues, the ellipse tip and die (ETD) and sub-path tip and die (STD) were proposed. In addition, based on the results of numerical analysis, the tip and die structures were manufactured and used to perform extrusion. Finally, we manufactured tubes that satisfied the target diameter, ovality, wall, and rib thickness using the newly proposed STD.
Enhancement of Adhesion Characteristics of Low-Density Polyethylene Using Atmospheric Plasma Initiated-Grafting of Polyethylene Glycol
Authors: Al-Gunaid Taghreed Abdulhameed , Krupa Igor , Ouederni Mabrouk , Krishnamoorthy Senthil Kumar , Popelka Anton
Published: April 2021

The low-density polyethylene/aluminum (LDPE/Al) joint in Tetra Pak provides stability and strength to food packaging, ensures protection against outside moisture, and maintains the nutritional values and flavors of food without the need for additives in the food products. However, a poor adhesion of LDPE to Al, due to its non-polar surface, is a limiting factor and extra polymeric interlayers or surface treatment is required. Plasma-assisted grafting of the LDPE surface with different molecular weight compounds of polyethylene glycol (PEG) was used to improve LDPE/Al adhesion. It was found that this surface modification contributed to significantly improve the wettability of the LDPE surface, as was confirmed by contact angle measurements. The chemical composition changes after plasma treatment and modification process were observed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). A surface morphology was analyzed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Adhesion characteristics of LDPE/Al adhesive joints were analyzed by the peel tests. The most significant adhesion improvement of the PEG modified LDPE surface was achieved using 10.0 wt.% aqueous (6000 M) PEG solution, while the peel resistance increased by approximately 54 times in comparison with untreated LDPE.
Biodegradation Process of PSF-PUR Blend Hollow Fiber Membranes Using Escherichia coli Bacteria—Evaluation of Changes in Properties and Porosity
Authors: Sikorska Wioleta , Milner-Krawczyk Małgorzata , Wasyłeczko Monika , Wojciechowski Cezary , Chwojnowski Andrzej
Published: April 2021

This work was focused on biodegradation with Escherichia coli bacteria studies of PSF-PUR blend semipermeable hollow fiber membranes that possibly can undergo a partial degradation process. Hollow fiber membranes were obtained from polysulfone (PSF) and polyurethane (PUR) containing ester bonds in the polymer chain in various weight ratios using two solvents: N,N-Dimethylmethanamide (DMF) or N-Methylpyrrolidone (NMP). The membranes that underwent the biodegradation process were tested for changes in the ultrafiltration coefficient (UFC), retention and cut-off point. Moreover, the membranes were subjected to scanning electron microscopy (SEM), MeMoExplorerTM Software and Fourier-transform infrared spectroscopy (FT-IR) analysis. The influence of E. coli and its metabolites has been proven by the increase in UFC after biodegradation and changes in the selectivity and porosity of individual membranes after the biodegradation process.