bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Atherogenic Dyslipidaemia and Lipid Triad and Scales That Assess Insulin Resistance
Authors: Paublini Hernán , López González Angel Arturo , Busquets-Cortés Carla , Tomas-Gil Pilar , Riutord-Sbert Pere , Ramírez-Manent José Ignacio
Published: April 2023

Background: Atherogenic dyslipidaemia (AD) and lipid triad (LT) are characterised by high triglyceride levels together with low HDL and normal or high LDL cholesterol and are favoured by a persistent state of insulin resistance (IR), which increases the release of free fatty acids from abdominal adipose tissue. This alteration in the lipid profile favours the accelerated development of atherosclerosis, which is the most important cause of morbidity and mortality in all countries in the developed and developing world. One of the elements that plays a major role in the genesis of AD is IR. The aim of this study was to determine the relationship between variables that assess atherogenic risk (AD and LT) and scales that assess the risk of presenting insulin resistance. Methods: A descriptive cross-sectional study of 418,343 workers was conducted to evaluate atherogenic dyslipidaemia and lipid triad; a relationship with three insulin resistance risk scales (Triglycerides/HDL, TyG index, METS-IR) was established. The usefulness of IR risk scales for predicting AD and LT was calculated by applying ROC curves, obtaining the area under the curve (AUC) and cut-off points with their sensitivity, specificity, and Youden index. Multivariate analysis was performed by binary logistic regression. Results: The prevalence of high-risk values for insulin resistance with all of the scales is much higher in people with AD and LT compared to those without. The ROC curves present us with an AUC with the three insulin resistance risk scales for the two dyslipidaemias studied with figures ranging between 0.856 and 0.991, which implies that the results are good/very good. Conclusions: A relationship between atherogenic dyslipidaemia and the three insulin resistance risk scales assessed is revealed, with higher IR mean values and prevalence in people with atherogenic dyslipidaemia and lipid triad. The three scales make it possible to adequately classify the presence of AD and LT. The highest AUC is presented by the triglycerides/HDL scale, with a result close to 1. METS-IR is the most recommended formula to estimate insulin resistance.
Physical Activity, Rather Than Diet, Is Linked to Lower Insulin Resistance in PCOS Women—A Case-Control Study
Authors: Jurczewska Justyna , Ostrowska Joanna , Chełchowska Magdalena , Panczyk Mariusz , Rudnicka Ewa , Kucharski Marek , Smolarczyk Roman , Szostak-Węgierek Dorota
Published: April 2023

Insulin resistance (IR) is a prominent feature of polycystic ovary syndrome (PCOS). The importance of lifestyle interventions in the management of PCOS is strongly highlighted and it is suggested that diet and physical activity may significantly influence insulin sensitivity. Therefore, we evaluated the link between diet and physical activity and various indices of insulin resistance, including adipokines secreted by the adipose tissue in 56 PCOS and 33 healthy control women. The original food frequency questionnaire and Actigraph GT3X-BT were used to assess the adherence to the diet recommended in IR and the level of physical activity, respectively. We observed that higher levels of physical activity were associated with lower HOMA-IR and a greater chance of its normal value in PCOS group. No such relationship was observed for other IR indices and adipokines or for the diet. However, we noted a strong correlation between HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and HOMA-AD (Homeostatic Model Assessment-Adiponectin) in PCOS women. Additionally, when we used HOMA-AD we observed a higher prevalence of IR among PCOS women. Our study supports the beneficial role of physical activity in the management of insulin resistance in PCOS women. Moreover, our findings indicate that HOMA-AD may be a promising surrogate marker for insulin resistance assessment in women with PCOS.
Gut Immunobiosis and Biomodulators
Authors: Miniello Vito Leonardo , Miniello Andrea , Ficele Laura , Skublewska-D’Elia Aleksandra , Dargenio Vanessa Nadia , Cristofori Fernanda , Francavilla Ruggiero
Published: April 2023

The human gastrointestinal (GI) tract hosts complex and dynamic populations of microorganisms (gut microbiota) in advantageous symbiosis with the host organism through sophisticated molecular cross-talk. The balance and diversification within microbial communities (eubiosis) are crucial for the immune and metabolic homeostasis of the host, as well as for inhibiting pathogen penetration. In contrast, compositional dysregulation of the microbiota (dysbiosis) is blamed for the determinism of numerous diseases. Although further advances in the so-called ‘omics’ disciplines are needed, dietary manipulation of the gut microbial ecosystem through biomodulators (prebiotics, probiotics, symbionts, and postbiotics) represents an intriguing target to stabilize and/or restore eubiosis. Recently, new approaches have been developed for the production of infant formulas supplemented with prebiotics (human milk oligosaccharides [HMOs], galacto-oligosaccharides [GOS], fructo-oligosaccharides [FOS]), probiotics, and postbiotics to obtain formulas that are nutritionally and biologically equivalent to human milk (closer to the reference).
Patients with Diverticular Disease Have Different Dietary Habits Compared to Control Subjects: Results from an Observational Italian Study
Authors: Polese Barbara , Carabotti Marilia , Rurgo Sara , Ritieni Camilla , Sarnelli Giovanni , Barbara Giovanni , Pace Fabio , Cuomo Rosario , Annibale Bruno ,   on behalf of REMAD Group
Published: April 2023

The role of dietary habits as risk factor for the development of diverticular complications has strongly emerged in the last years. We aimed to evaluate possible differences in dietary habits between patients with diverticular disease (DD) and matched controls without diverticula. Dietary habits were obtained from standardized food frequency questionnaires collected at entry to the Diverticular Disease Registry (REMAD). We compared controls (C) (n = 119) with asymptomatic diverticulosis (D) (n = 344), symptomatic uncomplicated diverticular disease (SUDD) (n = 154) and previous diverticulitis (PD) (n = 83) patients, in terms of daily calories, macro and micronutrients and dietary vitamins. Daily kcal intake and lipids, both saturated and unsaturated, were significantly lower in patients with DD than C. Total protein consumption was lower in PD than D, with differing consumption of unprocessed red meat, white meat and eggs between groups. Consumption of fibre, both soluble and insoluble, was lower in patients with PD compared to patients with SUDD, D and C, whereas dietary vitamins A, C, D and E and Oxygen Radical Adsorbance Capacity index were lower in all DD groups compared to C. This observational study showed that DD patients have different dietary habits, mainly in terms of caloric, fat, fibre and vitamin intake, compared to control subjects.
Beta-Glucans of Cereals: Functional and Technological Properties
Authors: Lante Anna , Canazza Elisa , Tessari Paolo
Published: April 2023

β-glucans are a polymeric dietary fiber characterized by β-(1,3) and β-(1,4) glycosidic bonds between glucose monomers. They are often used as thickeners, stabilizers, and fat substitutes in foods. The functional and technological quality of β-glucans is attributed to their origin/source, molecular weight, and structural properties. In particular, physical treatments such as drying, cooking, freezing, and refrigeration influence their molecular, morphological, and rheological characteristics. In addition to their useful technical qualities, β-glucans are recognized for their numerous beneficial impacts on human health. For this reason, the European Food Safety Authority (EFSA) has provided a positive opinion on health claims such as cholesterol lowering and hypoglycemic properties relating to oats and barley β-glucans. This paper provides insight into the properties of β-glucans and different treatments affecting their characteristics and then reviews the latest research on β-glucans as a functional ingredient for people with type 2 diabetes mellitus (T2DM).
Intrahousehold Food Intake Inequality by Family Roles and Age Groups
Authors: Asma Khatun Mst , Kotani Koji
Published: April 2023

Food intake inequality at the individual level is rarely analyzed in intrahousehold settings. We examine dietary diversity scores of household members with a focus on their family roles (fathers, mothers, sons, daughters and grandparents) and age groups (children, adults and elderly). Whereas theory suggests that members in a household should have equal dietary diversity by receiving a certain share of available foods, this research hypothesizes that they do not do so by their roles and/or age groups. We conduct questionnaire surveys, collecting sociodemographic information and dietary data by using a 24 h recall method of 3248 subjects in 811 households from 1 urban and 2 rural areas in Bangladesh. The statistical analysis demonstrates three findings. First, poor and rural people have lower dietary diversity than nonpoor and urban people, respectively. Second, grandparents (children) have lower dietary diversity than do fathers (adults), confirming the existence of intrahousehold food intake inequality by the roles and/or age groups, irrespective of poverty level and areas of residence. Third, father and mother educations are crucial determinants that raise the dietary diversity of household members; however, they do not resolve the inequality. Overall, it is suggested that awareness programs of dietary diversity shall be necessary with a target group of fathers and mothers for the betterment of intrahousehold inequality and health at the household level, contributing to sustainable development goals.
Virgin Olive Oil Ranks First in a New Nutritional Quality Score Due to Its Compositional Profile
Authors: García-González Aída , Quintero-Flórez Angelica , Ruiz-Méndez María-Victoria , Perona Javier S.
Published: April 2023

Dietary oils play a crucial role in maintaining a healthy diet. However, with the increasing number of oils available, it became a challenging task for food producers and consumers to select the best oil for their needs. In this work, an easy-to-understand nutrition quality score was created, using a model that included beneficial lipid compounds criteria according to the dietary recommendations published by international food and health organizations. The algorithm assigned points for each component of the model considering their content in each particular oil. The points were added up and the fats and oils were classified by the corresponding percentile. As a result, among the 32 edible oils that were evaluated, virgin olive oil ranked first with a score of 100. All plant oils, except for margarine and coconut oil, ranked above the 50th percentile. Receiver–operator curves and regression models showed that saturated fatty acids may be able to predict the score, and thus, the nutritional quality of the oils. In conclusion, the proposed nutritional quality score would promote healthy and nutritious food options for consumers and would provide food producers with a valuable tool to select high-quality oils for their products, ensuring that they meet the nutritional requirements.
Risk Assessment of Micronutrients Deficiency in Vegetarian or Vegan Children: Not So Obvious
Authors: Chouraqui Jean-Pierre
Published: April 2023

Vegetarian diets have gained in popularity worldwide and therefore an increasing number of children may be exposed to the resulting nutritional consequences. Among them, the risk of micronutrient shortfall is particularly of concern. This narrative review aims to assess and discuss the relevance of micronutrient deficiency risk based on the available data. It mainly draws attention to iron, zinc, iodine, and vitamins B12 and D intake. Diets that are more restrictive in animal source foods, such as vegan diets, have a greater likelihood of nutritional deficiencies. However, the actual risk of micronutrient deficiency in vegetarian children is relatively difficult to assert based on the limitations of evidence due to the lack of well-designed studies. The risk of vitamin B12 deficiency must be considered in newborns from vegan or macrobiotic mothers and children with the most restrictive diet, as well as the risk of iron, zinc, and iodine deficiency, possibly by performing the appropriate tests. A lacto-ovo-vegetarian diet exposes a low risk if it uses a very varied diet with a sufficient intake of dairy products. Vegan and macrobiotic diets should be avoided during pregnancy and childhood. There is a need for education and nutrition guidance and the need for supplementation should be assessed individually.
5-Chloro-2-Guanidinobenzimidazole (ClGBI) Is a Non-Selective Inhibitor of the Human HV1 Channel
Authors: Szanto Tibor G. , Feher Adam , Korpos Eva , Gyöngyösi Adrienn , Kállai Judit , Mészáros Beáta , Ovari Krisztian , Lányi Árpád , Panyi Gyorgy , Varga Zoltan
Published: April 2023

5-chloro-2-guanidinobenzimidazole (ClGBI), a small-molecule guanidine derivative, is a known effective inhibitor of the voltage-gated proton (H+) channel (HV1, Kd ≈ 26 μM) and is widely used both in ion channel research and functional biological assays. However, a comprehensive study of its ion channel selectivity determined by electrophysiological methods has not been published yet. The lack of selectivity may lead to incorrect conclusions regarding the role of hHv1 in physiological or pathophysiological responses in vitro and in vivo. We have found that ClGBI inhibits the proliferation of lymphocytes, which absolutely requires the functioning of the KV1.3 channel. We, therefore, tested ClGBI directly on hKV1.3 using a whole-cell patch clamp and found an inhibitory effect similar in magnitude to that seen on hHV1 (Kd ≈ 72 μM). We then further investigated ClGBI selectivity on the hKV1.1, hKV1.4-IR, hKV1.5, hKV10.1, hKV11.1, hKCa3.1, hNaV1.4, and hNaV1.5 channels. Our results show that, besides HV1 and KV1.3, all other off-target channels were inhibited by ClGBI, with Kd values ranging from 12 to 894 μM. Based on our comprehensive data, ClGBI has to be considered a non-selective hHV1 inhibitor; thus, experiments aiming at elucidating the significance of these channels in physiological responses have to be carefully evaluated.
Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin
Authors: Abouelkheir Mohamed , Taher Ibrahim , Eladl Amira S. R. , Shabaan Dalia A. , Soliman Mona F. M. , Taha Ahmed E.
Published: April 2023

Ethanol-producing dysbiotic gut microbiota could accelerate the progress of non-alcoholic fatty liver disease (NAFLD). Metformin demonstrated some benefits in NAFLD. In the present study, we tested the ability of metformin to modify ethanol-producing gut bacterial strains and, consequently, retard the progress of NAFLD. This 12-week study included forty mice divided into four groups (n = 10); normal diet, Western diet, Western diet with intraperitoneal metformin, and Western diet with oral metformin. Oral metformin has a slight advantage over intraperitoneal metformin in ameliorating the Western diet–induced changes in liver function tests and serum levels of different cytokines (IL-1β, IL-6, IL-17, and TNF-α). Changes in liver histology, fibrosis, lipid content, Ki67, and TNF-α were all corrected as well. Faecal ethanol contents were increased by the Western diet but did not improve after treatment with metformin although the numbers of ethanol-producing Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) were decreased by oral metformin. Metformin did not affect bacterial ethanol production. It does not seem that modification of ethanol-producing K. pneumoniae and E. coli bacterial strains by metformin could have a significant impact on the therapeutic potentials of metformin in this experimental model of NAFLD.
Anti-Alopecia Activity of Coumarin Derivatives Isolated from Merremia peltata Leaves and Computational Study of Their Binding to Androgen Receptors Using Molecular Docking and Molecular Dynamic Simulation
Authors: Abdurrahman Syawal , Ruslin Ruslin , Hasanah Aliya Nur , Ifaya Mus , Mustarichie Resmi
Published: April 2023

Alopecia is a condition in which hair on the scalp or other areas of the body is lost or falls out excessively. Nutritional deficiency causes blood flow to the head to decrease causing the hormone testosterone to be changed by the enzyme 5-α-reductase to dihydrotestosterone, which inhibits the growth phase and accelerates the death phase. One of the methods developed to treat alopecia is through inhibition of the 5-α-reductase enzyme, which converts testosterone to its more potent metabolite, dihydrotestosterone (DHT). Ethnomedicinally, Merremia peltata leaf is used by the people of Sulawesi as a remedy for baldness. Therefore, in this research, an in vivo study was conducted on rabbits to determine the anti-alopecia activity of M. peltata leaf compounds. The structure of the compounds isolated from the M. peltata leaf ethyl acetate fraction was determined by analysis of NMR and LC-MS data. An in silico study was then carried out using minoxidil as a comparison ligand; scopolin (1) and scopoletin (2) isolated from M. peltata leaf were identified as anti-alopecia compounds by predicting docking, simulating molecular dynamics and predicting absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox). Compounds 1 and 2 had a better effect on hair growth compared to positive controls, and NMR and LC-MS analysis showed that they had comparable binding energies to receptors in the molecular docking interaction study: −4.51 and −4.65 kcal/mol, respectively, compared to −4.8 kcal/mol for minoxidil. Molecular dynamics simulation analysis with the parameters binding free energy calculated using the MM-PBSA method and complex stability based on SASA, PCA, RMSD, and RMSF showed that scopolin (1) has a good affinity for androgens receptors. The ADME-Tox prediction for scopolin (1) showed good results for the parameters of skin permeability, absorption and distribution. Therefore, scopolin (1) is a potential antagonist to androgen receptors and could be useful in the treatment of alopecia.
Nanogel Containing Gamma-Oryzanol-Loaded Nanostructured Lipid Carriers and TiO2/MBBT: A Synergistic Nanotechnological Approach of Potent Natural Antioxidants and Nanosized UV Filters for Skin Protection
Authors: Badalkhani Omolbanin , Pires Patrícia C. , Mohammadi Maryam , Babaie Soraya , Paiva-Santos Ana Cláudia , Hamishehkar Hamed
Published: April 2023

The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently decreasing the chance of disease development. In the present study, a topical xanthan gum nanogel containing gamma-oryzanol-loaded nanostructured lipid carriers (NLCs) and nanosized UV filters TiO2 and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was developed to assess their synergistic potential in having multifunctional skin beneficial properties. The developed NLCs contained the natural-based solid lipids shea butter and beeswax, liquid lipid carrot seed oil, and the potent antioxidant gamma-oryzanol, with an optimum particle size for topical application (<150 nm), good homogeneity (PDI = 0.216), high zeta potential (−34.9 mV), suitable pH value (6), good physical stability, high encapsulation efficiency (90%), and controlled release. The final formulation, a nanogel containing the developed NLCs and the nano UV filters, showed high long-term storage stability and high photoprotection ability (SPF = 34) and resulted in no skin irritation or sensitization (rat model). Hence, the developed formulation showed good skin protection and compatibility, demonstrating promise as a new platform for the future generation of natural-based cosmeceuticals.
Electrospun Nanofibers for Dura Mater Regeneration: A Mini Review on Current Progress
Authors: Pant Bishweshwar , Park Mira , Kim Allison
Published: April 2023

Dural defects are a common problem in neurosurgical procedures and should be repaired to avoid complications such as cerebrospinal fluid leakage, brain swelling, epilepsy, intracranial infection, and so on. Various types of dural substitutes have been prepared and used for the treatment of dural defects. In recent years, electrospun nanofibers have been applied for various biomedical applications, including dural regeneration, due to their interesting properties such as a large surface area to volume ratio, porosity, superior mechanical properties, ease of surface modification, and, most importantly, similarity with the extracellular matrix (ECM). Despite continuous efforts, the development of suitable dura mater substrates has had limited success. This review summarizes the investigation and development of electrospun nanofibers with particular emphasis on dura mater regeneration. The objective of this mini-review article is to give readers a quick overview of the recent advances in electrospinning for dura mater repair.
Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis
Authors: Tsai Ya-Chu , Hung Chen-Yiu , Tsai Tsen-Fang
Published: April 2023

Background: Treatment of hidradenitis suppurativa (HS) is difficult and current guidelines are based mainly on expert opinion and non-randomized controlled trials. Recently, there have been some targeted therapies using uniform primary endpoints for outcome assessment. Objective: Recommendations can be provided on selecting biologics and targeted synthetic small molecules for refractory HS by comparing the efficacy and safety of these medications. Methods: Databases including ClinicalTrial.gov, Cochrane Library, and PubMed were searched. Randomized controlled trials (RCTs) for moderate-to-severe HS were eligible. We performed random-effect network meta-analysis and ranking probability. The primary outcome was Hidradenitis Suppurativa Clinical Response (HiSCR) at 12–16 weeks. Secondary outcome included Dermatology Life Quality Index (DLQI) 0/1, mean change of DLQI from baseline, and adverse effects. Results: A total of 12 RCTs involving 2915 patients were identified. Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w showed superiority to placebo in HiSCR at weeks 12 to 16. In addition, there was no significant difference between bimekizumab and adalimumab as measured by HiSCR (RR = 1.00; 95% CI: 0.66–1.52) and DLQI 0/1 (RR = 2.40, 95% CI: 0.88–6.50). In terms of ranking probability for achieving HiSCR at 12–16 weeks, adalimumab ranked first, followed by bimekizumab, secukinumab 300 mg q4w, and secukinumab 300 mg q2w. All biologics and small molecules did not differ in the development of adverse effects compared to placebo. Conclusions: Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w represent four regimens that produce better outcomes than placebo without increased risk of adverse events. Adalimumab and bimekizumab exhibited best HiSCR and DLQI 0/1 between weeks 12–16.
Zeolites as Ingredients of Medicinal Products
Authors: Souza Iane , García-Villén Fátima , Viseras César , Pergher Sibele
Published: April 2023

Development of new medicinal products for particular therapeutic treatment or for better manipulations with better quality and less side effects are possible as a result of advanced inorganic and organic materials application, among which zeolites, due to their properties and versatility, have been gaining attention. This paper is an overview of the development in the use of zeolite materials and their composites and modifications as medicinal products for several purposes such as active agents, carriers, for topical treatments, oral formulations, anticancer, the composition of theragnostic systems, vaccines, parenteral dosage forms, tissue engineering, etc. The objective of this review is to explore the main properties of zeolites and associate them with their drug interaction, mainly addressing the advances and studies related to the use of zeolites for different types of treatments due to their zeolite characteristics such as molecule storage capacity, physical and chemical stability, cation exchange capacity, and possibility of functionalization. The use of computational tools to predict the drug—zeolite interaction is also explored. As conclusion was possible to realize the possibilities and versatility of zeolite applications as being able to act in several aspects of medicinal products.
Core-Shell Structured PLGA Particles Having Highly Controllable Ketoprofen Drug Release
Authors: Varga Norbert , Bélteki Rita , Juhász Ádám , Csapó Edit
Published: April 2023

The non-steroid anti-inflammatory drug ketoprofen (KP) as a model molecule is encapsulated in different poly(lactide-co-glycolide) (PLGA) nanostructured particles, using Tween20 (TWEEN) and Pluronic F127 (PLUR) as stabilizers to demonstrate the design of a biocompatible colloidal carrier particles with highly controllable drug release feature. Based on TEM images the formation of well-defined core-shell structure is highly favorable using nanoprecipitation method. Stabile polymer-based colloids with ~200–210 nm hydrodynamic diameter can be formed by successful optimization of the KP concentration with the right choice of stabilizer. Encapsulation efficiency (EE%) of 14–18% can be achieved. We clearly confirmed that the molecular weight of the stabilizer thus its structure greatly controls the drug release from the PLGA carrier particles. It can be determined that ~20% and ~70% retention is available with the use of PLUR and TWEEN, respectively. This measurable difference can be explained by the fact that the non-ionic PLUR polymer provides a steric stabilization of the carrier particles in the form of a loose shell, while the adsorption of the non-ionic biocompatible TWEEN surfactant results in a more compact and well-ordered shell around the PLGA particles. In addition, the release property can be further tuned by decreasing the hydrophilicity of PLGA by changing the monomer ratio in the range of ~20–60% (PLUR) and 70–90% (TWEEN).
Permeability of Metformin across an In Vitro Blood–Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs)
Authors: Sharma Sejal , Zhang Yong , Akter Khondker Ayesha , Nozohouri Saeideh , Archie Sabrina Rahman , Patel Dhavalkumar , Villalba Heidi , Abbruscato Thomas
Published: April 2023

Our lab previously established that metformin, a first-line type two diabetes treatment, activates the Nrf2 pathway and improves post-stroke recovery. Metformin’s brain permeability value and potential interaction with blood–brain barrier (BBB) uptake and efflux transporters are currently unknown. Metformin has been shown to be a substrate of organic cationic transporters (Octs) in the liver and kidneys. Brain endothelial cells at the BBB have been shown to express Octs; thus, we hypothesize that metformin uses Octs for its transport across the BBB. We used a co-culture model of brain endothelial cells and primary astrocytes as an in vitro BBB model to conduct permeability studies during normoxia and hypoxia using oxygen–glucose deprivation (OGD) conditions. Metformin was quantified using a highly sensitive LC-MS/MS method. We further checked Octs protein expression using Western blot analysis. Lastly, we completed a plasma glycoprotein (P-GP) efflux assay. Our results showed that metformin is a highly permeable molecule, uses Oct1 for its transport, and does not interact with P-GP. During OGD, we found alterations in Oct1 expression and increased permeability for metformin. Additionally, we showed that selective transport is a key determinant of metformin’s permeability during OGD, thus, providing a novel target for improving ischemic drug delivery.
Surface Functionalised Parenteral Nanoemulsions for Active and Homotypic Targeting to Melanoma
Authors: Foglietta Federica , Bozza Annalisa , Ferraris Chiara , Cangemi Luigi , Bordano Valentina , Serpe Loredana , Martina Katia , Lazzarato Loretta , Pizzimenti Stefania , Grattarola Margherita , Cucci Marie Angele , Dianzani Chiara , Battaglia Luigi
Published: April 2023

Despite recent progressions in cancer genomic and immunotherapies, advanced melanoma still represents a life threat, pushing to optimise new targeted nanotechnology approaches for specific drug delivery to the tumour. To this aim, owing to their biocompatibility and favourable technological features, injectable lipid nanoemulsions were functionalised with proteins owing to two alternative approaches: transferrin was chemically grafted for active targeting, while cancer cell membrane fragments wrapping was used for homotypic targeting. In both cases, protein functionalisation was successfully achieved. Targeting efficiency was preliminarily evaluated using flow cytometry internalisation studies in two-dimensional cellular models, after fluorescence labelling of formulations with 6-coumarin. The uptake of cell-membrane-fragment-wrapped nanoemulsions was higher compared to uncoated nanoemulsions. Instead, the effect of transferrin grafting was less evident in serum-enriched medium, since such ligand probably undergoes competition with the endogenous protein. Moreover, a more pronounced internalisation was achieved when a pegylated heterodimer was employed for conjugation (p < 0.05).
Lactoferrin and Nanotechnology: The Potential for Cancer Treatment
Authors: Tran Tuan Hiep , Tran Phuong Thi Thu , Truong Duy Hieu
Published: April 2023

Lactoferrin (Lf)—a glycoprotein of the transferrin family—has been investigated as a promising molecule with diverse applications, including infection inhibition, anti-inflammation, antioxidant properties and immune modulation. Along with that, Lf was found to inhibit the growth of cancerous tumors. Owing to unique properties such as iron-binding and positive charge, Lf could interrupt the cancer cell membrane or influence the apoptosis pathway. In addition, being a common mammalian excretion, Lf offers is promising in terms of targeting delivery or the diagnosis of cancer. Recently, nanotechnology significantly enhanced the therapeutic index of natural glycoproteins such as Lf. Therefore, in the context of this review, the understanding of Lf is summarized and followed by different strategies of nano-preparation, including inorganic nanoparticles, lipid-based nanoparticles and polymer-based nanoparticles in cancer management. At the end of the study, the potential future applications are discussed to pave the way for translating Lf into actual usage.
A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia
Authors: Martín Roldán Alicia , Sánchez Suárez María Del Mar , Alarcón-Payer Carolina , Jiménez Morales Alberto , Puerta Puerta José Manuel
Published: April 2023

The therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might allow dose reduction or even treatment discontinuation. These strategies are often used in authentic practices to reduce adverse events, yet their impact on treatment-free remission (TFR) is a controversial debate. In some studies, it has been observed that as many as half of patients can achieve TFR after the discontinuation of TKI treatment. If TFR was more widespread and globally achievable, the perspective on toxicity could be changed. We retrospectively analysed 80 CML patients treated with tyrosine kinase inhibitor (TKI) at a tertiary hospital between 2002 and 2022. From them, 71 patients were treated with low doses of TKI, and 25 were eventually discontinued, 9 of them being discontinued without a previous dose reduction. Regarding patients treated with low doses, only 11 of them had molecular recurrence (15.4%), and the average molecular recurrence free survival (MRFS) was 24.6 months. The MRFS outcome was not affected by any of the variables examined, including gender, Sokal risk scores, prior treatment with interferon or hydroxycarbamide, age at the time of CML diagnosis, the initiation of low-dose therapy and the mean duration of TKI therapy. After TKI discontinuation, all but four patients maintained MMR, with a median follow-up of 29.2 months. In our study, TFR was estimated at 38.9 months (95% CI 4.1–73.9). This study indicates that low-dose treatment and/or TKI discontinuation is a salient, safe alternative to be considered for patients who may suffer adverse events (AEs), which hinder the adherence of TKI and/or deteriorate their life quality. Together with the published literature, it shows that it appears safe to administer reduced doses to patients with CML in the chronic phase. The discontinuation of TKI therapy once a DMR has been reached is one of the goals for these patients. The patient should be assessed globally, and the most appropriate strategy for management should be considered. Future studies are needed to ensure that this approach is included in clinical practice because of the benefits for certain patients and the increased efficiency for the healthcare system.
Hydrophobic Drug Carrier from Polycaprolactone-b-Poly(Ethylene Glycol) Star-Shaped Polymers Hydrogel Blend as Potential for Wound Healing Application
Authors: Ahmad Shariff Siti Hajar , Daik Rusli , Haris Muhammad Salahuddin , Ismail Mohamad Wafiuddin
Published: April 2023

Blending hydrogel with an amphiphilic polymer can increase the hydrophobic drug loading and entrapment efficiency of hydrogel-based formulations. In this study, a hydrogel formulation with star-shaped polycaprolactone-b-poly(ethylene glycol) (PCL-b-PEG) as the hydrophobic drug cargo is produced. The 4-arm and 6-arm star-shaped PCL are synthesized with different molecular weights (5000, 10,000, 15,000 g/mol) via ROP and MPEG as the hydrophilic segment is attached via the Steglich esterification. FTIR and 1H-NMR analysis showed the presence of all functional groups for homopolymers and copolymers. Mn for all synthesized polymers is close to the theoretical value while GPC spectra showed a monomodal peak with narrow molecular weight distribution (PDI:1.01–1.25). The thermal degradation temperature and crystalline melting point of synthesized polymers increase with the increase in molecular weight and number of arms. All formulations possess high drug loading and entrapment efficiency (>99%) and increase with increasing molecular weight, number of arms, and amount of polymer in the formulations. All formulations showed a sustained drug release pattern with no initial burst, which follows the Korsmeyer–Peppas kinetic model. The polymer hydrogel formulations showed antibacterial activity against E. coli and S. aureus. The hydrogel containing 4-arm PCL15k-PEG is chosen as the best formulation due to its high drug release, good antimicrobial activity, and morphology.
MXene-Functionalized Light-Induced Antimicrobial and Waterproof Polyacrylate Coating for Cementitious Materials Protection
Authors: Zhang Hongping , Tang Pengfei , Tang Youhong , Yang Kun , Wang Qingyuan
Published: April 2023

The penetration of external stimuli (microorganisms, ions, etc.) following to the pore is the key reason for the deterioration of cement and concrete structures. Although the traditional methods such as improving the chemical composition of cement and concrete materials can delay the erosion rate, the inevitable pore structure still makes its deterioration a challenge. Based on this, we reported a protective coating for cementitious materials based on phenol and Ti3C2 MXene-modified polyacrylate (MXene-PG/PA). The introduction of phenols enhanced the waterproof properties of polyacrylate by increasing the interaction among molecular chains. Moreover, the introduction of Ti3C2 MXene also endows the MXene-PG/PA coating with good light-induced antimicrobial properties. Beneficial to these designs, the MXene-PG/PA coating exhibited good waterproof properties (the water absorption ratio in seawater decreased by 58.2%) and antimicrobial properties (inhibition of E. coli and S. epidermidis activity under light). These results not only confirm that the MXene-PG/PA coating is a potential candidate of protective coating for cement-based materials, but also provide a new strategy for the design of multifunctional protective coatings.
Low Dielectric Constant Characteristics of Styrene and Maleimide Anhydride Copolymer with Modification for High Frequency Application of Printed Circuit Board
Authors: Lee Pilwoo , Jung Hunsang , Yoo Chan-Sei , Lee Hyun Ho
Published: April 2023

Recently, due to the intensive and fast progress of the high frequency wireless communication environment, including 5th generation (5G) wireless communication, more robust substrate for printed circuit board (PCB) application, especially with less power consumption, is required. In this study, modified resins based on styrene-maleic anhydride (SMA) copolymer were prepared and evaluated as binder resin to accomplish a low dielectric constant or relative permittivity (εr: <3.0) substrate for the PCB application under ultrahigh frequencies (UHF; 1 GHz~9.4 GHz). The low εr dielectric characteristics of the modified SMA copolymer could be correlated with effects from the stereo-structure of carbon chains or conformational orientation, where the degree of crystallization was analyzed by X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) spectroscopies. Prepreg films of the low εr modified SMA copolymers and their compounds with epoxy resins were also characterized in terms of dielectric loss or dissipation factor (Df), which have shown more noticeable relation with their stereo-structures as well.
Influence of Cross-Linking and Crystalline Morphology on the Shape-Memory Properties of PET/PEN/PCL Copolyesters Using Trimesic Acid and Glycerol
Authors: Yang Fu-Ting , Chen Yu-Ming , Rwei Syang-Peng
Published: April 2023

PCL-based biodegradable shape-memory polymers (SMPs) are limited in strength, which restricts their practical applications. In this study, a series of novel SMPs, composed of poly(ethylene terephthalate) (PET), poly(ethylene naphthalate) (PEN), and poly(ε-caprolactone) (PCL), were synthesized and cross-linked using planar (benzene-1,3,5-tricarboxylic acid, BTC) or non-planar (glycerol, GC) cross-linkers via the one-pot method. The influence of different kinds of cross-linkers and hard segments of copolyesters on the thermal properties, crystallization behavior, mechanical properties, shape-memory performance, and degradability was investigated by FT-IR, 1H-NMR, DSC, DMA, TGA, XRD, tensile test, intrinsic viscosity measurement, and in vitro enzymatic degradation test. The results indicate that the tensile strength of the copolyester can be significantly improved from 27.8 to 53.2 MPa by partially replacing PET with PEN while maintaining its shape-memory characteristics. Moreover, a small amount of cross-linking modification leads to higher temperature sensitivity, improved shape recovery rate at third round (Rr(3) = 99.1%), and biodegradability in the cross-linked PET/PEN/PCL shape-memory polymers. By changing the crystallization morphology and cross-linking forms of the material, we have developed a shape-memory polymer with both high strength and a high shape recovery rate, which provides a new strategy for the development of shape-memory materials.
Development of Three-Dimensional (3D) Biodegradable Polyglycolic Acid Fiber (PGA) Preforms for Scaffold Applications: Experimental Patterning and Fiber Volume Fraction-Porosity Modeling Study
Authors: Kundak Hikmet , Bilisik Kadir
Published: April 2023

Three-dimensional (3D) biodegradable polyglycolic acid fiber (PGA) preforms were developed as temporary scaffolds for three-dimensional tissue regeneration applications. Three-dimensional biodegradable polyglycolic acid fiber (PGA) preforms including various degrees of interlaced structures called 3D plain, semi-interlaced, and orthogonal woven preforms were designed. Analytical relations and finite element model-based software (TexGen) on fiber volume fraction and porosity fraction were proposed to predict scaffolds’ stiffness and strength properties considering micromechanics relations. It was revealed that yarn-to-yarn space, density, and angles of all 3D PGA fiber preforms were heterogeneous and demonstrated direction-dependent features (anisotropy). Total fiber volume fractions (Vfp) and porosity fraction (Vtpr) predicted by analytic and numerical modelling of all 3D scaffolds showed some deviations compared to the measured values. This was because yarn cross-sections in the scaffolds were changed from ideal circular yarn (fiber TOW) geometry to high-order ellipse (lenticular) due to inter-fiber pressure generated under a tensile-based macrostress environment during preform formation. Z-yarn modulus (Ez-yarn) and strength (σz-yarn) were probably critical values due to strong stiffness and strength in the through-the-thickness direction where hydrogel modulus and strengths were negligibly small. Morphology of the scaffold showed that PGA fiber sets in the preform were locally distorted, and they appeared as inconsistent and inhomogeneous continuous fiber forms. Additionally, various porosity shapes in the preform based on the virtual model featured complex shapes from nearly trapezoidal beams to partial or concave rectangular beams and ellipsoid rectangular cylinders. It was concluded that 3D polyglycolic acid fiber preforms could be a temporary supportive substrate for 3D tissue regeneration because cells in the scaffold’s thickness can grow via through-the-thickness fiber (z-yarn), including various possible mechanobiology mechanisms.
Innovative Collagen Based Biopolymers Tested as Fertilizers for Poor Soils Amendment
Authors: Constantin Carolina , Stefan Daniela Simina , Manea-Saghin Ana-Maria , Meghea Irina
Published: April 2023

Improving soil quality is of growing interest and, among optimal solutions, the reuse and recycling of biopolymers of pelt waste from the tannery industry have been proposed, one of them being for collagen hydrolysate with micronutrients and polymers incorporated, to be used as fertilizers for poor soils rehabilitation. As functionalization agents, polyacrylamide, starch and dolomite were included into biopolymer matrixes in order to enhance their specific efficiency. These fertilizers were adequately characterized for their physical–chemical properties, including nutrient content, and tested on three poor soils, while a fourth sample of normal soil was chosen for comparative purposes. These soils were also characterized for their texture and physical–chemical properties in order to establish the fertility state of the soils as a function of nutrient content. In this respect, a series of agrochemical tests were developed at laboratory scale, simulating real agriculture environments in a vegetation room, where a significant plant growth in height was observed for all the agro-hydrogels with nutrients encapsulated, and multiplication of the nodosities number was observed in the case of the soybean culture. The most significant effect was obtained in the case of the fertilizer functionalized with starch. Finally, the application dose of the organic fertilizers for specific culture plants was estimated, such as field cultures (cereals, corn), field vegetables, vineyards or fruit-growing plantations. These agro-collagen fertilizers are particularly recommended for amendment of field cereals and vegetables. The novelty of this study mainly consists of the recovery and recycling of the pelt waste as efficient fertilizers after their adequate functionalization with synthetic or natural biopolymers.
Buckling Analysis on Resin Base Laminated Plate Reinforced with Uniform and Functional Gradient Distribution of Carbon Fiber in Thermal Environment
Authors: Zhou Xiaoqiang , You Qingquan , Gao Yuan , Hua Fenfei , Fu Wanbiao , Huang Qingyang , Wang Yuanfang
Published: April 2023

The present paper aims to investigate the buckling load of functionally graded carbon-fiber-reinforced polymer (FG-CFRP) composite laminated plates under in-plane loads in a thermal environment. The effective material properties of the CFRP composite are calculated by the Mori–Tanaka homogenization method. The theoretical formulations are based on classical laminate plate theory (CLPT) and the von Kármán equations for large deflections. The governing equations are derived based on the principle of virtual work and then solved through the Navier solution. Results are obtained for the critical buckling load and temperature effect of a simply supported plate subjected to in-plane loading. A detailed numerical study is conducted to provide important insights into the effects of the functionally graded carbon fiber (CF) distribution pattern and volume fraction, total number of layers, temperature, geometrical dimension and lamination angle on the buckling load of functionally carbon-fiber-reinforced composite plates. Finally, the validation is compared with the Reddy and finite element analyses, which show consistency with each other.
The Analysis of Stress Raisers Affecting the GFRP Strength at Quasi-Static and Cyclic Loads by the Theory of Critical Distances, Digital Image Correlation, and Acoustic Emission
Authors: Lobanov Dmitrii , Yankin Andrey , Mullahmetov Maksim , Chebotareva Ekaterina , Melnikova Valeriya
Published: April 2023

The purpose of this work is to analyze the stress-raisers that affect the tensile strength and fatigue resistance of GFRP parts using the point and line methods of the theory of critical distances (TCD) to obtain a quantitative measure of the defect size that can be tolerated by the composite before it fails. In the course of the work, a method combining TCD and the Weibull function was developed. In the course of the work, GFRP structural fiberglass for electrical purposes was tested under uniaxial quasi-static and cyclic loading with digital image correlation (DIC) and acoustic emission (AE), as well as a numerical simulation of deformation. The studied specimens were plain (without a stress-raiser) and notched (V-shaped) with different notch root radii and depths. The results were used to determine the material critical distances. In this case, two approaches to TCD were used: line (LM) and point (PM) methods. To analyze the experimental results, finite element modeling was applied using the ANSYS software package. As a result, the linearized maximum principal stresses were obtained on the central line passing through the top of the stress raiser. Thus, the values of the critical distances of the material were determined by PM and LM. Based on the data obtained, the sizes of permissible defects in the studied fiberglass were established that do not affect the tensile and fatigue strength of the material. The paper illustrates the cumulative energy, peak amplitudes, and distributions of the frequency of the spectral maximum of acoustic emission signals obtained after the destruction of specimens by fatigue test. Evolutions of deformation fields on the specimen surface were recorded using a Vic-3D contactless optical video system and the DIC.