bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D Deficiency in Cushing’s Disease: Before and After Its Supplementation
Authors: Guarnotta Valentina , Di Gaudio Francesca , Giordano Carla
Published: February 2022

Background: The primary objective of the study was to assess serum 25-hydroxyvitamin D [25(OH)D] values in patients with Cushing’s disease (CD), compared to controls. The secondary objective was to assess the response to a load of 150,000 U of cholecalciferol. Methods: In 50 patients with active CD and 48 controls, we evaluated the anthropometric and biochemical parameters, including insulin sensitivity estimation by the homeostatic model of insulin resistance, Matsuda Index and oral disposition index at baseline and in patients with CD also after 6 weeks of cholecalciferol supplementation. Results: At baseline, patients with CD showed a higher frequency of hypovitaminosis deficiency (p = 0.001) and lower serum 25(OH)D (p < 0.001) than the controls. Six weeks after cholecalciferol treatment, patients with CD had increased serum calcium (p = 0.017), 25(OH)D (p < 0.001), ISI-Matsuda (p = 0.035), oral disposition index (p = 0.045) and decreased serum PTH (p = 0.004) and total cholesterol (p = 0.017) values than at baseline. Multivariate analysis showed that mean urinary free cortisol (mUFC) was independently negatively correlated with serum 25(OH)D in CD. Conclusions: Serum 25(OH)D levels are lower in patients with CD compared to the controls. Vitamin D deficiency is correlated with mUFC and values of mUFC > 240 nmol/24 h are associated with hypovitaminosis D. Cholecalciferol supplementation had a positive impact on insulin sensitivity and lipids.
Home Food Environment Changes and Dietary Intake during an Adolescent Behavioral Weight Loss Intervention Differ by Food Security Status
Authors: Adams Elizabeth L. , Caccavale Laura J. , LaRose Jessica Gokee , Raynor Hollie A. , Bean Melanie K.
Published: February 2022

Behavioral weight loss (BWL) for pediatric obesity includes guidance on improving the home food environment and dietary quality; yet food insecurity presents barriers to making these changes. This study examined if home food environment, dietary quality, energy intake, and body weight changes during adolescent obesity treatment differed by food security status, and if changes in the home food environment were associated with changes in dietary quality and energy intake by food security status. Adolescents (n = 82; 13.7 ± 1.2 years) with obesity participated in a 4-month BWL treatment. Food insecurity, home food environment (Home Food Inventory [HFI]), dietary quality (Healthy Eating Index [HEI]), energy intake, and body mass index (BMI) were assessed at baseline and post-treatment. A reduced obesogenic home food environment and improved dietary quality were observed for food secure (ps < 0.01), but not insecure households (ps > 0.05) (mean difference, HFI: −6.6 ± 6.4 vs. −2.4 ± 7.4; HEI: 5.1 ± 14.4 vs. 2.7 ± 17.7). Energy intake and BMI decreased for adolescents in food secure and insecure households (ps < 0.03) (mean difference; energy intake: −287 ± 417 vs. −309 ± 434 kcal/day; BMI: −1.0 ± 1.4 vs. −0.7 ± 1.4). BWL yielded similar reductions in energy intake and body weight yet did not offer the same benefits for improved dietary quality and the home food environment for adolescents with food insecurity.
Plasma Metabolite Profiles of Red Meat, Poultry, and Fish Consumption, and Their Associations with Colorectal Cancer Risk
Authors: Wang Fenglei , Chandler Paulette D. , Zeleznik Oana A. , Wu Kana , Wu You , Yin Kanhua , Song Rui , Avila-Pacheco Julian , Clish Clary B. , Meyerhardt Jeffrey A. , Zhang Xuehong , Song Mingyang , Ogino Shuji , Lee I-Min , Eliassen A. Heather , Liang Liming , Smith-Warner Stephanie A. , Willett Walter C. , Giovannucci Edward L.
Published: February 2022

Background: Red and processed meat consumption has been consistently associated with increased risk of colorectal cancer (CRC), but the association for fish intake is unclear. Evidence using objective dietary assessment approaches to evaluate these associations is sparse. Objectives: We aim to investigate the plasma metabolite profiles related to red meat, poultry, and fish consumption and examine their associations with CRC risk. Methods: We measured plasma metabolites among 5269 participants from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up study (HPFS). We calculated partial Spearman correlations between each metabolite and self-reported intake of seven red meat, poultry, and fish groups. Metabolite profile scores correlated to self-reported dietary intakes were developed using elastic net regression. Associations between self-reported intakes, metabolite profile scores, and subsequent CRC risk were further evaluated using conditional logistic regression among 559 matched (1:1) case-control pairs in NHS/HPFS and replicated among 266 pairs in Women’s Health Study. Results: Plasma metabolites, especially highly unsaturated lipids, were differentially associated with red meat and fish groups. Metabolite profile scores for each food group were significantly correlated with the corresponding self-reported dietary intake. A higher dietary intake of processed red meat was associated with a higher risk of CRC (pooled OR per 1 SD, 1.15; 95% CI: 1.03, 1.29). In contrast, higher metabolite profile scores for all fish groups, not dietary intakes, were consistently associated with a lower CRC risk: the pooled OR per 1 SD was 0.86 (95% CI: 0.78, 0.96) for total fish, 0.86 (95% CI: 0.77, 0.96) for dark meat fish, and 0.87 (95% CI: 0.78, 0.97) for canned tuna fish. No significant associations were found for other food groups. Conclusions: Red meat and fish intake exhibited systematically different plasma metabolite profiles. Plasma metabolite profile of fish intake was inversely associated with CRC risk.
Patterns of Food Assistance Program Participation, Food Insecurity, and Pantry Use among U.S. Households with Children during the COVID-19 Pandemic
Authors: Harper Kaitlyn , Belarmino Emily H. , Acciai Francesco , Bertmann Farryl , Ohri-Vachaspati Punam
Published: February 2022

This study aims to describe differences in participation in the Supplemental Nutrition Assistance Program (SNAP), Special Supplemental Nutrition Program for Women and Children (WIC), and school meal programs by household characteristics prior to and during the pandemic, and to examine the association of program participation with food security status and food pantry use. We analyze secondary data (n = 470) from an online survey collected in July/August 2020 using weighted multiple logistic regression models. Participation in SNAP declined among households with children in the first four months of the pandemic, while participation in WIC increased slightly, and participation in school meals remained unchanged. There were significant differences in SNAP, WIC, and school meal programs use by race/ethnicity, income, and urbanicity before and during the pandemic. Food insecurity prevalence was higher among SNAP participants at both periods but the gap between participants and non-participants was smaller during the pandemic. Pantry use and food insecurity rates were consistently higher among federal nutrition assistance program participants, possibly suggesting unmet food needs. These results highlight the need for increased program benefits and improved access to food, particularly during periods of hardship.
The Role of Multiply-Fortified Table Salt and Bouillon in Food Systems Transformation
Authors: Matthias Dipika , McDonald Christine M. , Archer Nicholas , Engle-Stone Reina
Published: February 2022

Our global food system lacks the critically needed micronutrients to meet the daily requirements of the most at-risk populations. Diets also continue to shift toward unhealthy foods, including the increased intake of salt. While most countries exceed the WHO’s recommended levels, sodium does play an essential physiological role. Table salt and other salt-containing condiments, such as bouillon, also have cultural importance, as they are used to enhance the flavor of foods cooked at home. Given their universal consumption across income classes and both urban and rural populations, these condiments are an integral part of the food system and should, therefore, be part of its transformation. Fortification of salt and salt-containing condiments can play a catalytic role in the delivery of population-wide nutritional and health benefits. With relatively consistent levels of intake across the population, these condiments hold high potential for delivering micronutrients beyond iodine while also reducing concerns related to high micronutrient intake, particularly so in countries where the industries are relatively consolidated. As a flexible and complementary strategy to an evolving food system, fortification levels can also be adjusted over time to ensure micronutrient delivery targets continue to be achieved as the system improves, whether through lower intakes of sodium in line with WHO recommendations, enhanced consumption of nutrient-dense foods, and/or broader adoption of biofortified crops. Future areas of innovation are required to realize this vision, including developing affordable salt substitutes to meet cost requirements of consumers in low-and middle-income countries, improving the stability and bioavailability of the micronutrients in condiments so that delivery targets can be reached without affecting sensory attributes, and the development of efficient systems for monitoring population intake and micronutrient status to inform fortification program design and management. Rather than being considered antithetical to the transformation, multiply-fortified salt and bouillon can strengthen our ability to meet the cultural, sensory, nutritional, and health needs of an evolving food system.
Dietary Patterns and Risk of Chronic Obstructive Pulmonary Disease among Chinese Adults: An 11-Year Prospective Study
Authors: Yu Wei , Pan Lang , Cao Weihua , Lv Jun , Guo Yu , Pei Pei , Xia Qingmei , Du Huaidong , Chen Yiping , Yang Ling , Chen Junshi , Yu Canqing , Chen Zhengming , Li Liming ,   on behalf of China Kadoorie Biobank Collaborative Group
Published: February 2022

The evidence about the association between dietary patterns and the incidence of chronic obstructive pulmonary disease (COPD) among Chinese adults is limited. In the present study, we analyzed the prospective data of 421,426 participants aged 30–79 years from the China Kadoorie Biobank. Factor analysis with a principal component method was employed to identify dietary patterns. Cox proportional hazard regression models were performed to explore the association between dietary patterns and incident COPD. Two dietary patterns were identified: the traditional northern dietary pattern was characterized by a low intake of rice and a high intake of wheat and other staple foods, while the balanced dietary pattern was characterized by a high intake of fresh fruit and protein-rich foods (soybean, meat, poultry, fish, eggs, and dairy products). During a median follow-up of 11.13 years, 5542 men and 5750 women developed COPD. After adjustments for potential confounders, the balanced dietary pattern was associated with a lower risk of COPD (p for trend <0.001), with a hazard ratio (95% confidence interval) of 0.75 (0.67, 0.84) for those in the highest quintile compared with those in the lowest quintile. Such association was modified by sex, smoking status, and adiposity level.
Impact of Parenteral Glutamine Supplement on Oncologic Outcomes in Patients with Nasopharyngeal Cancer Treated with Concurrent Chemoradiotherapy
Authors: Wang Chih-Chun , Hwang Tzer-Zen , Yang Chuan-Chien , Lien Ching-Feng , Wang Chien-Chung , Shih Yu-Chen , Yeh Shyh-An , Hsieh Meng-Che
Published: February 2022

Background: Oral mucositis (OM) is a common toxic side effect in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) that has a negative impact on treatment outcomes and patients’ survival. Our study aimed to evaluate the impact of parenteral glutamine supplement (dipeptiven) on oncologic outcomes in patients with NPC treated with CCRT. Methods: Patients who were diagnosed with pathologically proved NPC and treated with CCRT were enrolled into our study. Patients were classified as dipeptiven (+) and dipeptiven (–). Oncologic outcomes were measured, and multivariate regression analysis was performed. Grade 3–4 treatment related toxicities were also documented. Results: A total of 144 patients with NPC were recruited in this study to evaluate oncologic outcomes, with 41 dipeptiven (+) and 103 dipeptiven (–). CCRT interruption rate and severe adverse effect (SAE) rate were significant lower in the dipeptiven (+) group than in the dipeptiven (–) group. The median overall survival (OS) was not mature yet in the dipeptiven (+) group and 30 months in the dipeptiven (–) group (p < 0.01). Multivariate analysis demonstrated that dipeptiven supplementation and CCRT interruption were independent predictors associated with better survival. The OS was longest in patients with a dipeptiven supplement and patients who had CCRT interruption had significantly worst OS. As for safety profiles, grade 3 to 4 adverse effects were fewer in dipeptiven (+) than in dipeptiven (–). Conclusion: Dipeptiven supplementation is crucial in NPC patients treated with CCRT, which can ameliorate treatment-related toxicity and augment treatment efficacy. Further prospective clinical trials are warranted to validate our results.
Phenotypes and Endotypes of Peach Allergy: What Is New?
Authors: Barni Simona , Caimmi Davide , Chiera Fernanda , Comberiati Pasquale , Mastrorilli Carla , Pelosi Umberto , Paravati Francesco , Marseglia Gian Luigi , Arasi Stefania
Published: February 2022

Peach allergy is emerging as a common type of fresh-fruit allergy in Europe, especially in the Mediterranean area. The clinical manifestations of peach allergy tend to have a peculiar geographical distribution and can range from mild oral symptoms to anaphylaxis, depending on the allergic sensitization profile. The peach allergen Pru p 7, also known as peamaclein, has recently been identified as a marker of peach allergy severity and as being responsible for peculiar clinical features in areas with high exposure to cypress pollen. This review addresses the latest findings on molecular allergens for the diagnosis of peach allergy, the clinical phenotypes and endotypes of peach allergy in adults and children, and management strategies, including immunotherapy, for peach allergy.
The Prevalence of Overweight Status among Early Adolescents from Private Schools in Indonesia: Sex-Specific Patterns Determined by School Urbanization Level
Authors: Sarintohe Eveline , Larsen Junilla K. , Burk William J. , Vink Jacqueline M.
Published: February 2022

(1) Background: Few studies have investigated (demographic) correlates of (prevalent) overweight rates among early adolescents, especially from higher socioeconomic positions (SEP) in developing countries, such as Indonesia. The current study aims to fill this gap. (2) Methods: Participants included 411 adolescents from five private schools in Indonesia. Adolescents’ weight and height were measured, and adolescents completed questionnaires on demographic factors (i.e., sex, school area, ethnicity, pocket money) and previous year dieting. (3) Results: Results showed that more than one-third of the sample was overweight, with higher rates among adolescent males (47%) than females (24%). Moreover, adolescents attending schools in urban areas (compared with suburban areas), and those reporting past dieting (compared with those reporting no dieting) had higher overweight rates. Ethnicity and the amount of pocket money were not related to overweight status. Finally, a clear sex-specific interaction was found involving school area, showing that males in urban areas had a significantly higher risk to be overweight, whereas this did not apply to females. (4) Conclusions: males from urban area private schools in Indonesia may be an important target group for future preventive overweight interventions.
Malnutrition and Biomarkers: A Journey through Extracellular Vesicles
Authors: Mendivil-Alvarado Herminia , Sosa-León Leopoldo Alberto , Carvajal-Millan Elizabeth , Astiazaran-Garcia Humberto
Published: February 2022

Extracellular vesicles (EVs) have been identified as active components in cellular communication, which are easily altered both morphologically and chemically by the cellular environment and metabolic state of the body. Due to this sensitivity to the conditions of the cellular microenvironment, EVs have been found to be associated with disease conditions, including those associated with obesity and undernutrition. The sensitivity that EVs show to changes in the cellular microenvironment could be a reflection of early cellular alterations related to conditions of malnutrition, which could eventually be used in the routine monitoring and control of diseases or complications associated with it. However, little is known about the influence of malnutrition alone; that is, without the influence of additional diseases on the heterogeneity and specific content of EVs. To date, studies in “apparently healthy” obese patients show that there are changes in the size, quantity, and content of EVs, as well as correlations with some metabolic parameters (glucose, insulin, and serum lipids) in comparison with non-obese individuals. In light of these changes, a direct participation of EVs in the development of metabolic and cardiovascular complications in obese subjects is thought to exist. However, the mechanisms through which this process might occur are not yet fully understood. The evidence on EVs in conditions of undernutrition is limited, but it suggests that EVs play a role in the maintenance of homeostasis and muscle repair. A better understanding of how EVs participate in or promote cellular signaling in malnutrition conditions could help in the development of new strategies to treat them and their comorbidities.
Healthy Immunity on Preventive Medicine for Combating COVID-19
Authors: Manna Pulak R. , Gray Zackery C. , Reddy P. Hemachandra
Published: February 2022

Immunomodulation is influenced by the consumption of nutrients, and healthy immunity is pivotal to defending an individual from a variety of pathogens. The immune system is a network of intricately regulated biological processes that is comprised of many organs, cellular structures, and signaling molecules. A balanced diet, rich in vitamins, minerals, and antioxidants, is key to a strengthened immune system and, thus, crucial to proper functioning of various physiological activities. Conversely, deficiencies of these micronutrients, involving impaired immunity, are linked to numerous health complications, along with a host of pathologies. Coronavirus disease 2019 (COVID-19) is a dangerous infectious disease caused by a β-form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its genomic variants, which enter host cells upon binding to the angiotensin converting enzyme 2 receptors, and is associated with substantial morbidities and mortalities globally. Patients afflicted with COVID-19 display asymptomatic to severe symptoms, occurrences of which are multifactorial and include diverse immune responses, sex and gender differences, aging, and underlying medical conditions. Geriatric populations, especially men in comparison to women, regardless of their states, are most vulnerable to severe COVID-19-associated infections and complications, with fatal outcomes. Advances in genomic and proteomic technologies help one understand molecular events, including host–pathogen interactions and pathogenesis of COVID-19 and, subsequently, have developed a variety of preventive measures urgently, ranging from mask wearing to vaccination to medication. Despite these approaches, no unique strategy is available today that can effectively prevent and/or treat this hostile disease. As a consequence, the maintenance of a boosted immune system could be considered a high priority of preventive medicine for combating COVID-19. Herein, we discuss the current level of understanding underlining the contribution of healthy immunity and its relevance to COVID-19 molecular pathogenesis, and potential therapeutic strategies, in the management of this devastating disease.
2-Styrylchromones: Cytotoxicity and Modulation of Human Neutrophils’ Oxidative Burst
Authors: Lucas Mariana , Freitas Marisa , Zanchetta Marco , Silva Artur M. S. , Fernandes Eduarda , Ribeiro Daniela
Published: February 2022

Neutrophils are polymorphonuclear leukocytes recruited to sites of acute inflammation, in response to pathogen invasion and tissue injury. The modulation of their activity, especially oxidative burst, may be important to control the inflammatory process. 2-Styrylchromones (2-SC) are derived from chromones and despite their recognized multiple biological activities, their anti-inflammatory and antioxidant properties are still poorly explored. Therefore, in this study, 43 structurally related 2-SC were evaluated concerning their effects on freshly isolated human neutrophils’ viability and oxidative burst. The studied 2-SC were divided into eight groups according to their substitution at C-4′ on B-ring (none, -OH, -OCH3, -OBn, -CH3, and -NO2), existence and location of -Cl on B-ring, and presence of -Br at C-3 on C-ring. Overall, most of the studied 2-SC did not affect neutrophils’ viability, at physiological relevant concentrations. The ones belonging to B group were the most effective (IC50 values < 2 μM), and present one -OH group at C-4′ or a catechol group at C-3′ and C-4′ on B-ring. These substituents seem to play an important role in the modulatory activity of human neutrophils’ oxidative burst. These results reinforce the great potential of 2-SC’s scaffold for the development of new anti-inflammatory agents.
Iodine Nanoparticles (Niodx™) for Radiotherapy Enhancement of Glioblastoma and Other Cancers: An NCI Nanotechnology Characterization Laboratory Study
Authors: Hainfeld James F. , Ridwan Sharif M. , Stanishevskiy Yaroslav , Smilowitz Henry M.
Published: February 2022

Effective and durable treatment of glioblastoma is an urgent unmet medical need. In this article, we summarize a novel approach of a physical method that enhances the effectiveness of radiotherapy. High atomic number nanoparticles that target brain tumors are intravenously administered. Upon irradiation, the nanoparticles absorb X-rays creating free radicals, increasing the tumor dose several fold. Radiotherapy of mice with orthotopic human gliomas and human triple negative breast cancers growing in the brain showed significant life extensions when the nanoparticles were included. An extensive study of the properties of the iodine-containing nanoparticle (Niodx) by the Nanotechnology Characterization Laboratory, including sterility, physicochemical characterization, in vitro cytotoxicity, in vivo immunological characterization, and in vivo toxicology, is presented. In summary, the iodine nanoparticle Niodx appears safe and effective for translational studies toward human use.
Creating Acceptable Tablets 3D (CAT 3D): A Feasibility Study to Evaluate the Acceptability of 3D Printed Tablets in Children and Young People
Authors: Bracken Louise , Habashy Rober , McDonough Emma , Wilson Fiona , Shakeshaft Joanne , Ohia Udeme , Garcia-Sorribes Tamar , Isreb Abdullah , Alhnan Mohamed A. , Peak Matthew
Published: February 2022

3D printing (3DP) has been proposed as a novel approach for personalising dosage forms for children and young people (CYP). Owing to its low cost and the lack of need for finishing steps, fused deposing modelling (FDM) 3DP has been heavily researched in solid dosage forms (SDFs) manufacturing. However, the swallowability and overall acceptability of 3D printed dosage forms are yet to be established. This work is the first to evaluate the acceptability of different sized 3D printed placebo SDFs in CYP (aged 4–12 years). All participants had previously participated in a feasibility study (CAT study) that assessed the swallowability and acceptability of different sized GMP manufactured placebo conventional film-coated tablets, and therefore only attempted to swallow one 3D printed tablet. The participants assessed the swallowability, acceptability, mouthfeel, volume of water consumed, and taste of the sample using a 5-point hedonic facial scale on a participant questionnaire. A total of 30 participants were recruited, 87% of whom successfully swallowed the 3D printed tablet that they attempted to take. Attributes of the 3D printed tablets were scored as acceptable by the following percentage of participants—swallowability (80%), mouthfeel/texture (87%), the volume of water consumed (80%), taste (93%), and overall acceptability (83%). Overall, 77% of children reported they would be happy to take the tablet every day if it was a medicine. Participants were also asked which tablets felt better in the mouth—the film-coated tablets or the 3D printed tablets, and the most popular response (43%) was that both were acceptable. This study shows that FDM-based 3D printed SDFs may be a suitable dosage form for children aged 4–12 years. The results from this feasibility study will be used to inform a larger, definitive study looking at the acceptability of 3D printed tablets in children.
Prodrug Therapies for Infectious and Neurodegenerative Diseases
Authors: Markovic Milica , Deodhar Suyash , Machhi Jatin , Yeapuri Pravin , Saleh Maamoon , J. Edagwa Benson , Mosley Rodney Lee , Gendelman Howard E.
Published: February 2022

Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.
Human Lactobacillus Biosurfactants as Natural Excipients for Nasal Drug Delivery of Hydrocortisone
Authors: Corazza Elisa , Abruzzo Angela , Giordani Barbara , Cerchiara Teresa , Bigucci Federica , Vitali Beatrice , di Cagno Massimiliano Pio , Luppi Barbara
Published: February 2022

The inclusion of a chemical permeation enhancer in a dosage form is considered an effective approach to improve absorption across the nasal mucosa. Herein we evaluated the possibility of exploiting biosurfactants (BS) produced by Lactobacillus gasseri BC9 as innovative natural excipients to improve nasal delivery of hydrocortisone (HC). BC9-BS ability to improve HC solubility and the BS mucoadhesive potential were investigated using the surfactant at a concentration below and above the critical micelle concentration (CMC). In vitro diffusion studies through the biomimetic membrane PermeaPad® and the same synthetic barrier functionalized with a mucin layer were assessed to determine BC9-BS absorption enhancing properties in the absence and presence of the mucus layer. Lastly, the diffusion study was performed across the sheep nasal mucosa using BC9-BS at a concentration below the CMC. Results showed that BC9-BS was able to interact with the main component of the nasal mucosa, and that it allowed for a greater solubilization and also permeation of the drug when it was employed at a low concentration. Overall, it seems that BC9-BS could be a promising alternative to chemical surfactants in the nasal drug delivery field.
Iontophoresis of Biological Macromolecular Drugs
Authors: Hasan Mahadi , Khatun Anowara , Kogure Kentaro
Published: February 2022

Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.
Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent
Authors: Nirosha Yalamandala Bhanu , Chen Pin-Hua , Moorthy Thrinayan , Huynh Thi My Hue , Chiang Wen-Hsuan , Hu Shang-Hsiu
Published: February 2022

Nano-catalytic agents actuating Fenton-like reaction in cancer cells cause intratumoral generation of reactive oxygen species (ROS), allowing the potential for immune therapy of tumor metastasis via the recognition of tumor-associated antigens. However, the self-defense mechanism of cancer cells, known as autophagy, and unsustained ROS generation often restricts efficiency, lowering the immune attack, especially in invading metastatic clusters. Here, a functional core-shell metal-organic framework nanocube (dual MOF) doubling as a catalytic agent and T cell infiltration inducer that programs ROS and inhibits autophagy is reported. The dual MOF integrated a Prussian blue (PB)-coated iron (Fe2+)-containing metal-organic framework (MOF, MIL88) as a programmed peroxide mimic in the cancer cells, facilitating the sustained ROS generation. With the assistance of Chloroquine (CQ), the inhibition of autophagy through lysosomal deacidification breaks off the self-defense mechanism and further improves the cytotoxicity. The purpose of this material design was to inhibit autophagy and ROS efficacy of the tumor, and eventually improve T cell recruitment for immune therapy of lung metastasis. The margination and internalization-mediated cancer cell uptake improve the accumulation of dual MOF of metastatic tumors in vivo. The effective catalytic dual MOF integrated dysfunctional autophagy at the metastasis elicits the ~3-fold recruitment of T lymphocytes. Such synergy of T cell recruitment and ROS generation transported by dual MOF during the metastases successfully suppresses more than 90% of tumor foci in the lung.
Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives
Authors: Tanase Daniela Maria , Apostol Alina Georgiana , Costea Claudia Florida , Tarniceriu Claudia Cristina , Tudorancea Ionut , Maranduca Minela Aida , Floria Mariana , Serban Ionela Lacramioara
Published: February 2022

Arterial hypertension (HTN) is one of the most prevalent entities globally, characterized by increased incidence and heterogeneous pathophysiology. Among possible etiologies, oxidative stress (OS) is currently extensively studied, with emerging evidence showing its involvement in endothelial dysfunction and in different cardiovascular diseases (CVD) such as HTN, as well as its potential as a therapeutic target. While there is a clear physiological equilibrium between reactive oxygen species (ROS) and antioxidants essential for many cellular functions, excessive levels of ROS lead to vascular cell impairment with decreased nitric oxide (NO) availability and vasoconstriction, which promotes HTN. On the other hand, transcription factors such as nuclear factor erythroid factor 2-related factor 2 (Nrf2) mediate antioxidant response pathways and maintain cellular reduction–oxidation homeostasis, exerting protective effects. In this review, we describe the relationship between OS and hypertension-induced endothelial dysfunction and the involvement and therapeutic potential of Nrf2 in HTN.
Effect of Dispersing Multiwalled Carbon Nanotubes and Graphene Nanoplatelets Hybrids in the Matrix on the Flexural Fatigue Properties of Carbon/Epoxy Composites
Authors: Jen Yi-Ming , Ni Wei-Lun
Published: February 2022

The synergistic effect of applying hybrid nanoparticles in improving the fatigue property of fiber reinforced polymer composites has rarely been explored before. Hence the monotonic and fatigue flexure properties of the carbon fiber reinforced epoxy laminates with matrix modified by multiwalled carbon nanotubes and graphene nanoplatelets were experimentally studied herein. The nanofiller ratio applied in the matrix modification was considered as a variable in the experimental program to investigate the effect of nanofiller ratio on the studied mechanical properties. A synergistic index has been employed to evaluate the synergistic effect of hybrid nanoparticles on the studied properties successfully. Experimental results show that the laminates with matrix modified under a nanofiller ratio (multiwalled carbon nanotube: graphene nanoplatelet) of 9:1 have the higher monotonic and fatigue strengths than those modified under other nanofiller ratios. The monotonic flexural strength and fatigue limit of the specimens modified under a nanofiller ratio of 9:1 are higher than the neat laminate specimens by 9.3 and 11.0%, respectively. The fatigue limits of the studied nano-modified laminates increase with the static strengths. Adding hybrid nanoparticles under proper nanofiller ratios in the matrix can suppress the degradation of the stiffness, further increase the resistance to fatigue damage. Examining the fracture surfaces of fatigued specimens reveals that the pullout/bridging effects of carbon nanotubes and the crack deflection effect of graphene nanoplatelets are the main reinforcement mechanisms in enhancing the fatigue strength of the composites.
Evaluation of the Performance of a ZnO-Nanoparticle-Coated Hydrocolloid Patch in Wound Healing
Authors: Le Van Anh Thi , Trinh Tung X. , Chien Pham Ngoc , Giang Nguyen Ngan , Zhang Xin-Rui , Nam Sun-Young , Heo Chan-Yeong
Published: February 2022

Hydrocolloid dressings are an important method for accelerating wound healing. A combination of a hydrocolloid and nanoparticles (NPs), such as gold (Au), improves the wound healing rate, but Au-NPs are expensive and unable to block ultraviolet (UV) light. Herein, we combined zinc oxide nanoparticles (ZnO-NPs) with hydrocolloids for a less expensive and more effective UV-blocking treatment of wounds. Using Sprague–Dawley rat models, we showed that, during 10-day treatment, a hydrocolloid patch covered with ZnO-NPs (ZnO-NPs-HC) macroscopically and microscopically stimulated the wound healing rate and improved wound healing in the inflammation phase as shown by reducing of pro-inflammatory cytokines (CD68, IL-8, TNF-α, MCP-1, IL-6, IL-1β, and M1) up to 50%. The results from the in vitro models (RAW264.7 cells) also supported these in vivo results: ZnO-NPs-HCs improved wound healing in the inflammation phase by expressing a similar level of pro-inflammatory mediators (TNF-α and IL-6) as the negative control group. ZnO-NPs-HCs also encouraged the proliferation phase of the healing process, which was displayed by increasing expression of fibroblast biomarkers (α-SMA, TGF-β3, vimentin, collagen, and M2) up to 60%. This study provides a comprehensive analysis of wound healing by measuring the biomarkers in each phase and suggests a cheaper method for wound dressing.
Formulation of Chitosan-Coated Apigenin Bilosomes: In Vitro Characterization, Antimicrobial and Cytotoxicity Assessment
Authors: Imam Syed Sarim , Alshehri Sultan , Altamimi Mohammad A. , Almalki Raed Khalid Hassan , Hussain Afzal , Bukhari Sarah I. , Mahdi Wael A. , Qamar Wajhul
Published: February 2022

We prepared apigenin (APG)-loaded bilosomes (BLs) and evaluated them for vesicle size, zeta-potential and encapsulation efficiency. The formulations were prepared with cholesterol (CHL), sodium deoxy cholate (SDC), Tween 80 (T80) and phosphatidylcholine (PC) using solvent evaporation method. The prepared formulations showed the optimum result was coated with much mucoadhesive polymer chitosan (CH, 0.25 and 0.5% w/v). The chitosan-coated bilosomes (CH-BLs) were further evaluated for surface morphology, drug–polymer interaction, mucoadhesion, permeation, antimicrobial activity and cell viability. The prepared APG-BLs showed nano-metric size (211 ± 2.87 nm to 433 ± 1.98 nm), polydispersibility index <0.5, negative zeta potential (−15 to −29 mV) and enhanced encapsulation efficiency (69.5 ± 0.93 to 81.9 ± 1.3%). Based on these findings, selected formulation (F2) was further coated with chitosan and showed a marked increase in vesicle size (298 ± 3.56 nm), a positive zeta potential (+17 mV), superior encapsulation efficiency (88.1 ± 1.48%) and improved drug release (69.37 ± 1.34%). Formulation F2C1 showed significantly enhanced permeation and mucoadhesion (p < 0.05) compared to formulation F2 due to the presence of CH as a mucoadhesive polymer. The presence of CH on the surfaces of BLs helps to open the tight membrane junctions and leads to enhanced permeation. A TEM study revealed non-aggregated smooth surface vesicles. The antimicrobial and cell viability assessment revealed better effects in terms of zone of inhibition and cell line assessment against two different cancer cell line. From the study, it can be concluded that APG-CHBLs could be a superior alternative to conventional delivery systems.
Optimization of Thermal and Mechanical Properties of Polypropylene-Wollastonite Composite Drawn Fibers Based on Surface Response Analysis
Authors: Leontiadis Konstantinos , Tsioptsias Costas , Messaritakis Stavros , Terzaki Aikaterini , Xidas Panagiotis , Mystikos Kyriakos , Tzimpilis Evangelos , Tsivintzelis Ioannis
Published: February 2022

The thermal and mechanical properties of polypropylene-wollastonite composite drawn fibers were optimized via experiments selected with the Box-Behnken approach. The drawing ratio, the filler and the compatibilizer content were chosen as design variables, while the tensile strength, the melting enthalpy and the onset decomposition temperature were set as response variables. Drawn fibers with tensile strength up to 535 MPa were obtained. Results revealed that the drawing ratio is the most important factor for the enhancement of tensile strength, followed by the filler content. All the design variables slightly affected the melting temperature and the crystallinity of the matrix. Also, it was found that the addition of polypropylene grafted with maleic anhydride as compatibilizer has a multiple effect on the final properties, i.e., it induces the dispersion of both the antioxidant and the filler, tending to increase thermal stability and tensile strength, while, on the same time, deteriorates mechanical and thermal properties due to its lower molecular weight and thermal stability. Such behavior does not allow for simultaneous maximization of thermal stability and tensile strength. Optimization based on a compromise, i.e., targeting maximization of tensile strength and onset decomposition temperature higher than 300 °C, yields high desirability values and predictions in excellent agreement with verification experiments.
Thermosensitive Polymers and Thermo-Responsive Liposomal Drug Delivery Systems
Authors: Abuwatfa Waad H. , Awad Nahid S. , Pitt William G. , Husseini Ghaleb A.
Published: February 2022

Temperature excursions within a biological milieu can be effectively used to induce drug release from thermosensitive drug-encapsulating nanoparticles. Oncological hyperthermia is of particular interest, as it is proven to synergistically act to arrest tumor growth when combined with optimally-designed smart drug delivery systems (DDSs). Thermoresponsive DDSs aid in making the drugs more bioavailable, enhance the therapeutic index and pharmacokinetic trends, and provide the spatial placement and temporal delivery of the drug into localized anatomical sites. This paper reviews the fundamentals of thermosensitive polymers, with a particular focus on thermoresponsive liposomal-based drug delivery systems.
Recent Progress on Heparin–Protamine Particles for Biomedical Application
Authors: Hata Yuuki , Miyazaki Hiromi , Ishihara Masayuki , Nakamura Shingo
Published: February 2022

Biomolecules are attractive building blocks with self-assembly ability, structural diversity, and excellent functionality for creating artificial materials. Heparin and protamine, a clinically relevant pair of biomolecules used in cardiac and vascular surgery, have been shown to coassemble into particulate polyelectrolyte complexes in vitro. The resulting heparin–protamine particles exhibit adhesive properties that enable advantageous interactions with proteins, cells, and various other substances and have been employed as functional materials for biomedical applications. In this review article, we summarize recent progress in research on the use of heparin–protamine particles as drug carriers, cell adhesives, and cell labels. Studies have demonstrated that heparin–protamine particles are potentially versatile in biomedical fields from drug delivery and regenerative medicine to plastic surgery.
Vertical Alignment of Liquid Crystals on Phenylphenoxymethyl-Substituted Polystyrene—PS Derivatives Structurally Similar to LC Molecules
Authors: Moon Jihyeon , Kang Chaewon , Kang Hyo
Published: February 2022

A series of polystyrene derivatives containing precursors of liquid crystal (LC) molecules, phenylphenoxymethyl-substituted polystyrene (PPHE#; # = 5, 15, 25, 50, 75, and 100)—where # is the molar content of 4-phenylphenol using polymer modification reactions—were prepared in order to examine the effect of the polymer film, which possess similar LC molecular structure on the LC alignment properties. It was found that the Tg values of the PPHE# were higher than 100 °C due to their aromatic structure in the biphenyl-based PHE moiety. The LC cells fabricated with PPHE5 and PPHE15 films exhibited planar LC alignment. Conversely, LC molecules showed a vertical alignment in LC cells made using the polymer films with phenylphenoxymethyl side groups in the range of 25–100 mol %. The polar surface energies on the PPHE# films can be associated with the vertical LC alignment on the PPHE# films. For example, vertical LC alignment was exhibited when the polar surface energy of the polymer films was less than approximately 4.2 mJ/m2. Aligning stability was observed at 200 °C and UV irradiation of 20 J/cm2 for LC cells made using the PPHE100 film. Therefore, it was found that biphenyl, one of the LC precursors, modified polystyrene derivatives and can produce a next-generation vertical LC alignment system.
A Complex In Vitro Degradation Study on Polydioxanone Biliary Stents during a Clinically Relevant Period with the Focus on Raman Spectroscopy Validation
Authors: Loskot Jan , Jezbera Daniel , Zmrhalová Zuzana Olmrová , Nalezinková Martina , Alferi Dino , Lelkes Krisztina , Voda Petr , Andrýs Rudolf , Fučíková Alena Myslivcová , Hosszú Tomáš , Bezrouk Aleš
Published: February 2022

Biodegradable biliary stents are promising treatments for biliary benign stenoses. One of the materials considered for their production is polydioxanone (PPDX), which could exhibit a suitable degradation time for use in biodegradable stents. Proper material degradation characteristics, such as sufficient stiffness and disintegration resistance maintained for a clinically relevant period, are necessary to ensure stent safety and efficacy. The hydrolytic degradation of commercially available polydioxanone biliary stents (ELLA-CS, Hradec Králové, Czech Republic) in phosphate-buffered saline (PBS) was studied. During 9 weeks of degradation, structural, physical, and surface changes were monitored using Raman spectroscopy, differential scanning calorimetry, scanning electron microscopy, and tensile and torsion tests. It was found that the changes in mechanical properties are related to the increase in the ratio of amorphous to crystalline phase, the so-called amorphicity. Monitoring the amorphicity using Raman spectroscopy has proven to be an appropriate method to assess polydioxanone biliary stent degradation. At the 1732 cm−1 Raman peak, the normalized shoulder area is less than 9 cm−1 which indicates stent disintegration. The stent disintegration started after 9 weeks of degradation in PBS, which agrees with previous in vitro studies on polydioxanone materials as well as with in vivo studies on polydioxanone biliary stents.
Influence of Polymer Viscoelasticity on Microscopic Remaining Oil Production
Authors: Yan Yiqun , Wang Lihui , Sang Guoqiang , Han Xu
Published: February 2022

To investigate the impact of polymer viscoelasticity on microscopic remaining oil production, this study used microscopic oil displacement visualisation technology, numerical simulations in PolyFlow software, and core seepage experiments to study the viscoelasticity of polymers and their elastic effects in porous media. We analysed the forces affecting the microscopic remaining oil in different directions, and the influence of polymer viscoelasticity on the displacement efficiency of microscopic remaining oil. The results demonstrated that the greater the viscosity of the polymer, the greater the deformation and the higher the elasticity proportion. In addition, during the creep recovery experiment at low speed, the polymer solution was mainly viscous, while at high speed it was mainly elastic. When the polymer viscosity reached 125 mPa·s, the core effective permeability reached 100 × 10−3 μm2, and the equivalent shear rate exceeded 1000 s−1, the polymer exhibited an elastic effect in the porous medium and the viscosity curve displayed an ‘upward’ phenomenon. Moreover, the difference in the normal deviatoric stress and horizontal stress acting on the microscopic remaining oil increased exponentially as the viscosity of the polymer increased. The greater the viscosity of the polymer, the greater the remaining oil deformation. During the microscopic visualisation flooding experiment, the viscosity of the polymer, the scope of the mainstream line, and the recovery factor all increased. The scope of spread in the shunt line area significantly increased, but the recovery factor was significantly lower than that in the mainstream line. The amount of remaining oil in the unaffected microscopic area also decreased.