bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Dietary Intake Estimated by Web-Based Dietary Assessment Methods and Usability Using Dietary Records or 24-h Dietary Recalls: A Scoping Review
Authors: Murai Utako , Tajima Ryoko , Matsumoto Mai , Sato Yoko , Horie Saki , Fujiwara Aya , Koshida Emiko , Okada Emiko , Sumikura Tomoko , Yokoyama Tetsuji , Ishikawa Midori , Kurotani Kayo , Takimoto Hidemi
Published: April 2023

The goal was to summarize studies comparing the accuracy of web-based dietary assessments with those of conventional face-to-face or paper-based assessments using 24-h dietary recall or dietary record methods in the general population. Using two databases, mean differences and correlation coefficients (CCs) for intakes of energy, macronutrients, sodium, vegetables, and fruits were extracted from each study independently by the authors. We also collected information regarding usability from articles reporting this. From 17 articles included in this review, the mean dietary intake differences in the web-based dietary assessment compared to conventional methods, were −11.5–16.1% for energy, −12.1–14.9% for protein, −16.7–17.6% for fat, −10.8–8.0% for carbohydrates, −11.2–9.6% for sodium, −27.4–3.9% for vegetables, and −5.1–47.6% for fruits. The CC was 0.17–0.88 for energy, protein, fat, carbohydrates, and sodium, and 0.23–0.85 for vegetables and fruits. In three out of four studies reporting usability, more than half of the participants preferred the web-based dietary assessment. In conclusion, % difference and CC of dietary intake were acceptable in both web-based dietary records and 24-h dietary recalls. The findings from this review highlight the possibility of wide-spread application of the web-based dietary assessment in the future.
Beverage Consumption Patterns and Nutrient Intake Are Associated with Cardiovascular Risk Factors among Urban Mexican Young Adults
Authors: Salinas-Mandujano Rocío Guadalupe , Laiseca-Jácome Estefany , Ramos-Gómez Minerva , Reynoso-Camacho Rosalía , Salgado Luis Miguel , Anaya-Loyola Miriam Aracely
Published: April 2023

Regular consumption of sugar-sweetened beverages has been related to metabolic diseases. Our objective was to identify beverage consumption patterns, nutrient intake, and their possible association with the prevalence of cardiovascular risk factors among Mexican young adults. A cross-sectional survey was conducted. Beverage consumption patterns were obtained by principal components analysis. Logistic regression models were applied to assess the association between the beverage patterns and cardiovascular risk factors. Four beverage patterns were identified. Higher consumption of alcoholic beverages was associated with lower odds for high body fat percent (OR: 0.371; 95% CI: 0.173–0.798), high blood pressure (OR: 0.318; 95% CI: 0.116–0.871), and high glucose (OR: 0.232; 95% CI: 0.061–0.875). Higher consumption of yogurt was associated with lower odds for high glucose (OR: 0.110; 95% CI: 0.22–0.559). In contrast, highest consumption of juice had greater odds for high triglycerides (OR: 1.084; 95% CI: 1.011–4.656). Higher consumption of milk was associated with greater odds for high glucose (OR: 5.304; 95% CI: 1.292–21.773). Beverage consumption habits in Mexican young adults are associated with increased risk factors for cardiovascular disease. Therefore, intervening during young adulthood should be considered in order to improve current health and prevent cardiovascular mortality in later decades.
Fruit and Vegetable Intake and Home Nutrition Environment among Low-Income Minority Households with Elementary-Aged Children
Authors: Naylor Metoyer Brittni , Chuang Ru-Jye , Lee MinJae , Markham Christine , Brown Eric , Almohamad Maha , Dave Jayna , Sharma Shreela
Published: April 2023

Racial/ethnic and socioeconomic differences were shown to have an influence on child fruit and vegetable intake. This study examined the associations between parent and child fruit and vegetable intake and the home nutrition environment among Hispanic/Latino and African American families. Through a cross-sectional study design, self-reported surveys (n = 6074) were obtained from adult–child dyad participants enrolled in Brighter Bites, an evidence-based health promotion program, in the fall of 2018. For every once/day increase in frequency of parent FV intake, there was an increase in child FV intake by 0.701 times/day (CI: 0.650, 0.751, p < 0.001) and 0.916 times/day (CI: 0.762, 1.07; p < 0.001) among Hispanic/Latinos and African Americans, respectively. In Hispanic/Latino participants, significant positive associations were found between fruits as well as vegetables served at mealtimes ≥3 times/week (p < 0.001), family mealtimes 7 times/week (p = 0.018), parent–child communication about healthy eating and nutrition at least sometimes during the past 6 months (p < 0.05), and frequency of child FV intake, after adjusting for covariates. In African American participants, a significant positive association was found in fruits served at mealtimes ≥1 times/week (p < 0.05), and vegetables served at mealtimes ≥5 times/week (p < 0.05). Meals cooked from scratch a few times a day/all the time were significantly positively associated with frequency of child FV intake for both Hispanic/Latino (p = 0.017) and African American (p = 0.007) groups. The relationship between home nutrition environment and child FV intake varied by race and ethnicity. Future programs should consider designing culturally tailored interventions to address racial/ethnic-specific influences that match the child’s race, culture, and ethnicity.
Role of Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 in the Wound Healing Process of the Excisional Skin
Authors: Panagiotou Dimitrios , Filidou Eirini , Gaitanidou Maria , Tarapatzi Gesthimani , Spathakis Michail , Kandilogiannakis Leonidas , Stavrou George , Arvanitidis Konstantinos , Tsetis Joulia , Gionga Persefoni , Shrewsbury Anne , Manolopoulos Vangelis , Kapoukranidou Dora , Lasithiotakis Konstantinos , Kolios George , Kotzampassi Katerina
Published: April 2023

The probiotics Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 seem to promote wound healing when applied topically. Our aim was to investigate their effect on the mRNA expression of pro-inflammatory, healing and angiogenetic factors during the healing process of a standardized excisional wound model in rats. Rats subjected to six dorsal skin wounds were allocated to Control; L. plantarum; combined formula of L. rhamnosus plus B. longum; L. rhamnosus; and B. longum treatments, applied every two days, along with tissue collection. The pro-inflammatory, wound-healing, and angiogenetic factors of mRNA expression were assessed by qRT-PCR. We found that L. plantarum exerts a strong anti-inflammatory effect in relation to L. rhamnosus–B. longum, given alone or in combination; the combined regime of L. rhamnosus–B. longum, works better, greatly promoting the expression of healing and angiogenic factors than L. plantarum. When separately tested, L. rhamnosus was found to work better than B. longum in promoting the expression of healing factors, while B. longum seems stronger than L. rhamnosus in the expression of angiogenic factors. We, therefore, suggest that an ideal probiotic treatment should definitively contain more than one probiotic strain to speed up all three healing phases.
Socio-Demographic, Behavioral and Psychological Factors Associated with High BMI among Adults in a Southeast Asian Multi-Ethnic Society: A Structural Equation Model
Authors: Chew Han Shi Jocelyn , Loong Shaun Seh Ern , Lim Su Lin , Tam Wai San Wilson , Chew Nicholas W. S. , Chin Yip Han , Chao Ariana M. , Dimitriadis Georgios K. , Gao Yujia , So Bok Yan Jimmy , Shabbir Asim
Published: April 2023

While various influencing factors of overweight and obesity have been identified, the underlying mechanism remains unclear. We examined the relationships among sociodemographic, behavioral, and psychological factors on anthropometry in a multi-ethnic population with overweight and obesity. Participants (N = 251) were recruited from January to October 2022. Mean age and self-reported BMI were 31.7 ± 10.1 years and 29.2 ± 7.2 kg/m2. Participants were mostly female (52.4%) and overweight (58.2%). Multivariate multiple regression was performed using maximum likelihood estimation. Body mass index was associated with waist circumference, age, sex, race, marital status, education level, residential region, overeating habit, immediate thinking, self-regulation, and physical activity, but not anxiety, depression, or the intention to change eating habits. Final model indicated good fit: χ2 (30, N = 250) = 33.5, p = 0.32, CFI = 0.993, TLI = 0.988, RMSEA = 0.022, and SRMR = 0.041. Direct effects were found between BMI and overeating (β = 0.10, p = 0.004), race (β = −0.82, p < 0.001), marital status (β = −0.42, p = 0.001), and education level (β = −0.28, p = 0.019). Crisps (68.8%), cake (66.8%) and chocolate (65.6%) were identified as the most tempting foods. Immediate thinking indirectly increased overeating habits through poor self-regulation, although sociodemographic characteristics better predicted anthropometry than psycho-behavioral constructs.
Nursing Students’ Preferences for Learning Medical and Bioscience Subjects: A Qualitative Study
Authors: Kyte Lars , Lindaas Ingrid , Dahl Hellen , Valaker Irene , Kleiven Ole T. , Sægrov Solveig
Published: April 2023

(1) Background: There are considerable challenges and concerns related to learning medical and bioscience subjects (MBS) in nursing education and integrating this knowledge into nursing. The aim of this study was to explore what learning methods nursing students prefer when studying MBS, and how this learning may be enhanced to facilitate the integration of these subjects into nursing. (2) Methods: Individual interviews with 10 nursing students. Transcripts from the interviews were analysed by systematic text condensation and the COREQ checklist for qualitative studies was completed. (3) Results: Students prefer varied and active learning methods in MBS. The participants in the study highlighted both organised tutorials in groups and working with fellow students outside of organised teaching. All participants used educational videos. Learning MBS by drawing was appreciated both during lectures and in student-initiated colloquia. Strategies that favour in-depth learning were appreciated, and it was found that lectures did not have to cover the entire curriculum. Teachers’ attitudes toward students also were seen to have a considerable impact on students’ motivation for learning. (4) Conclusion: Applying active learning methods and focusing on the most relevant topics in MBS appears to improve students’ ability to integrate this knowledge into nursing; teachers should also be aware of their role as a motivator.
Strengths Model-Based Nursing Interventions for Inpatients in Psychiatric Inpatient Settings Using a Seclusion Room: A Case Series Study
Authors: Nagayama Yutaka , Tanaka Koji , Oe Masato
Published: April 2023

The use of coercive measures in psychiatric inpatient settings has been an important issue for many years. Nursing interventions based on a strengths model could enable a reduction in the use of these measures. This study aimed to describe the practice of nursing interventions using a strengths model for psychiatric inpatients who have been in seclusion for a long time. We also constructed a nursing model to minimize coercive measures. The participants were eight inpatients who had been in seclusion for a long time. Nursing interventions based on a strengths model were implemented in collaboration with nurses from six long-term care units in three psychiatric hospitals in Japan. For 4 of the 8 participants, the seclusion time decreased by 20–45%. However, for another 2, it increased by about 23–34%. An average decrease of 9.6% was observed, and the open observation time increased by 1.4 h per day on the seclusion days. When using this model, the nurses considered the effects of stimulating strengths. We believe this approach may promote inpatients’ self-insight. Considering the perspective of stimulus adjustment might be useful for maximizing the positive effects of working on strengths.
CT Radiomics and Clinical Feature Model to Predict Lymph Node Metastases in Early-Stage Testicular Cancer
Authors: Lisson Catharina , Manoj Sabitha , Wolf Daniel , Schrader Jasper , Schmidt Stefan , Beer Meinrad , Goetz Michael , Zengerling Friedemann , Lisson Christoph
Published: April 2023

Accurate retroperitoneal lymph node metastasis (LNM) prediction in early-stage testicular germ cell tumours (TGCTs) harbours the potential to significantly reduce over- or undertreatment and treatment-related morbidity in this group of young patients as an important survivorship imperative. We investigated the role of computed tomography (CT) radiomics models integrating clinical predictors for the individualised prediction of LNM in early-stage TGCT. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. Dedicated radiomics software was used to segment 273 retroperitoneal lymph nodes and extract features. After feature selection, radiomics-based machine learning models were developed to predict LN metastasis. The robustness of the procedure was controlled by 10-fold cross-validation. Using multivariable logistic regression modelling, we developed three prediction models: a radiomics-only model, a clinical-only model, and a combined radiomics–clinical model. The models’ performances were evaluated using the area under the receiver operating characteristic curve (AUC). Finally, decision curve analysis was performed to estimate the clinical usefulness of the predictive model. The radiomics-only model for predicting lymph node metastasis reached a greater discrimination power than the clinical-only model, with an AUC of 0.87 (±0.04; 95% CI) vs. 0.75 (±0.08; 95% CI) in our study cohort. The combined model integrating clinical risk factors and selected radiomics features outperformed the clinical-only and the radiomics-only prediction models, and showed good discrimination with an area under the curve of 0.89 (±0.03; 95% CI). The decision curve analysis demonstrated the clinical usefulness of our proposed combined model. The presented combined CT-based radiomics–clinical model represents an exciting non-invasive tool for individualised LN metastasis prediction in testicular germ cell tumours. Multi-centre validation is required to generate high-quality evidence for its clinical application.
IL17RB and IL17REL Expression Are Associated with Improved Prognosis in HPV-Infected Head and Neck Squamous Cell Carcinomas
Authors: Sun Yuhan , Khan Md. Abdullah Al Kamran , Mangiola Stefano , Barrow Alexander David
Published: April 2023

Changes in the cellular secretome are implicated in virus infection, malignancy, and anti-tumor immunity. We analyzed the association between transcriptional signatures (TS) from 24 different immune and stromal cell types on the prognosis of HPV-infected and HPV-free head and neck squamous carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) cohort. We found that HPV-positive HNSCC patients have tumors with elevated immune cell TS and improved prognosis, which was specifically associated with an increased tumor abundance of memory B and activated natural killer (NK) cell TS, compared to HPV-free HNSCC patients. HPV-infected patients upregulated many transcripts encoding secreted factors, such as growth factors, hormones, chemokines and cytokines, and their cognate receptors. Analysis of secretome transcripts and cognate receptors revealed that tumor expression of IL17RB and IL17REL are associated with a higher viral load and memory B and activated NK cell TS, as well as improved prognosis in HPV-infected HNSCC patients. The transcriptional parameters that we describe may be optimized to improve prognosis and risk stratification in the clinic and provide insights into gene and cellular targets that may potentially enhance anti-tumor immunity mediated by NK cells and memory B cells in HPV-infected HNSCC patients.
Characterization of Pseudofusicoccum Species from Diseased Plantation-Grown Acacia mangium, Eucalyptus spp., and Pinus massoniana in Southern China
Authors: Li Guoqing , Wu Wenxia , Lu Linqin , Chen Bingyin , Chen Shuaifei
Published: April 2023

Fungi from Pseudofusicoccum (Phyllostictaceae, Botryosphaeriales) have been reported as pathogens, endophytes, or saprophytes from various woody plants in different countries. Recently, Botryosphaeriales isolates were obtained from the dead twigs of Acacia mangium, Eucalyptus spp., Pinus massoniana, and Cunninghamia lanceolata in Guangdong, Guangxi, Hainan, and Fujian Provinces in southern China. This study aimed to understand the diversity, distribution, and virulence of these Pseudofusicoccum species on these trees. A total of 126 Pseudofusicoccum isolates were obtained, and the incidences of Pseudofusicoccum (percentage of trees that yielded Pseudofusicoccum) on A. mangium, P. massoniana, Eucalyptus spp., and C. lanceolata were 21%, 2.6%, 0.5%, and 0%, respectively. Based on the internal transcribed spacer (ITS), translation elongation factor 1-alpha (tef1), and β-tubulin (tub2) loci, 75% of the total isolates were identified as P. kimberleyense, and the remaining isolates were identified as P. violaceum. For P. kimberleyense, the majority of isolates (83%) were from A. mangium, and the rest were from P. massoniana (14%) and Eucalyptus spp. (3%). Similarly, the proportion of isolates of P. violaceum from A. mangium, P. massoniana, and Eucalyptus spp. were 84%, 13%, and 3%, respectively. Inoculation trials showed that the two species produced expected lesions on the tested seedlings of A. mangium, E. urophylla × E. grandis, and P. elliottii. This study provides fundamental information on Pseudofusicoccum associated with diseases in main plantations in southern China.
NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized Children
Authors: Sorrentino Leonardo , Toscanelli Walter , Fracella Matteo , De Angelis Marta , Frasca Federica , Scagnolari Carolina , Petrarca Laura , Nenna Raffaella , Midulla Fabio , Palamara Anna Teresa , Nencioni Lucia , Pierangeli Alessandra
Published: April 2023

Respiratory diseases caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) are frequent causes of the hospitalization of children; nonetheless, RSV is responsible for the most severe and life-threatening illnesses. Viral infection triggers an inflammatory response, activating interferon (IFN)-mediated responses, including IFN-stimulated genes (ISG) expression with antiviral and immunomodulatory activities. In parallel, the reactive oxygen species (ROS) production activates nuclear factor erythroid 2-related factor 2 (NRF2), whose antioxidant activity can reduce inflammation by interacting with the NF-kB pathway and the IFN response. To clarify how the interplay of IFN and NRF2 may impact on clinical severity, we enrolled children hospitalized for bronchiolitis and pneumonia, and measured gene expression of type-I and III IFNs, of several ISGs, of NRF2 and antioxidant-related genes, i.e., glucose-6-phosphate dehydrogenase (G6PD), heme oxygenase 1 (HO1), and NAD(P)H dehydrogenase [Quinone] 1 (NQO1) in RSV- (RSV-A N = 33 and RSV-B N = 30) and HRV (N = 22)-positive respiratory samples. NRF2 and HO1 expression is significantly elevated in children with HRV infection compared to RSV (p = 0.012 and p = 0.007, respectively), whereas ISG15 and ISG56 expression is higher in RSV-infected children (p = 0.016 and p = 0.049, respectively). Children admitted to a pediatric intensive care unit (PICU) had reduced NRF2 expression (p = 0.002). These data suggest, for the first time, that lower activation of the NRF2 antioxidant response in RSV-infected infants may contribute to bronchiolitis severity.
Fabrication of Nanoformulation Containing Carvedilol and Silk Protein Sericin against Doxorubicin Induced Cardiac Damage in Rats
Authors: Shariq Mohammad , Mahmood Tarique , Kushwaha Poonam , Parveen Saba , Shamim Arshiya , Ahsan Farogh , Wani Tanveer , Zargar Seema , Wasim Rufaida , Wahajuddin Muhammad
Published: April 2023

Nanotechnology has emerged as an inspiring tool for the effective delivery of drugs to help treat Coronary heart disease (CHD) which represents the most prevalent reason for mortality and morbidity globally. The current study focuses on the assessment of the cardioprotective prospective ofanovel combination nanoformulation of sericin and carvedilol. Sericin is a silk protein obtained from Bombyx mori cocoon and carvedilol is a synthetic nonselective β-blocker. In this present study, preparation of chitosan nanoparticles was performed via ionic gelation method and were evaluated for cardioprotective activity in doxorubicin (Dox)-induced cardiotoxicity. Serum biochemical markers of myocardial damage play a substantial role in the analysis of cardiovascular ailments and their increased levels have been observed to be significantly decreased in treatment groups. Treatment groups showed a decline in the positivity frequency of the Troponin T test as well. The NTG (Nanoparticle Treated Group), CSG (Carvedilol Standard Group), and SSG (Sericin Standard Group) were revealed to have reduced lipid peroxide levels (Plasma and heart tissue) highly significantly at a level of p < 0.01 in comparison with the TCG (Toxic Control Group). Levels of antioxidants in the plasma and the cardiac tissue were also established to be within range of the treated groups in comparison to TCG. Mitochondrial enzymes in cardiac tissue were found to be elevated in treated groups. Lysosomal hydrolases accomplish a significant role in counteracting the inflammatory pathogenesis followed by disease infliction, as perceived in the TCG group. These enzyme levels in the cardiac tissue were significantly improved after treatment with the nanoformulation. Total collagen content in the cardiac tissue of the NTG, SSG, and CSG groups was established to be highly statistically significant at p < 0.001 as well as statistically significant at p < 0.01, respectively. Hence, the outcomes of this study suggest that the developed nanoparticle formulation is effective against doxorubicin-induced cardiotoxicity.
A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result
Authors: Kikushima Wataru , Sakurada Yoichi , Fukuda Yoshiko , Matsubara Mio , Kotoda Yumi , Sugiyama Atsushi , Kashiwagi Kenji
Published: April 2023

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4–8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1–2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10−7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10−3 and 1.0 × 10−3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept.
Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options
Authors: Kumar Akash , Pramanik Jhilam , Goyal Nandani , Chauhan Dimple , Sivamaruthi Bhagavathi Sundaram , Prajapati Bhupendra G. , Chaiyasut Chaiyavat
Published: April 2023

The gut microbiota is critical for maintaining human health and the immunological system. Several neuroscientific studies have shown the significance of microbiota in developing brain systems. The gut microbiota and the brain are interconnected in a bidirectional relationship, as research on the microbiome–gut–brain axis shows. Significant evidence links anxiety and depression disorders to the community of microbes that live in the gastrointestinal system. Modified diet, fish and omega-3 fatty acid intake, macro- and micro-nutrient intake, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, and 5-HTP regulation may all be utilized to alter the gut microbiota as a treatment approach. There are few preclinical and clinical research studies on the effectiveness and reliability of various therapeutic approaches for depression and anxiety. This article highlights relevant research on the association of gut microbiota with depression and anxiety and the different therapeutic possibilities of gut microbiota modification.
Benzydamine—An Affordable Over-the-Counter Drug with Psychoactive Properties—From Chemical Structure to Possible Pharmacological Properties
Authors: Ősz Bianca-Eugenia , Jîtcă George , Sălcudean Andreea , Rusz Carmen Maria , Vari Camil-Eugen
Published: April 2023

Benzydamine is a non-steroidal anti-inflammatory drug with distinct pharmacological properties from other compounds in the same therapeutic class. The differences are structural and pharmacological in nature; the anti-inflammatory mechanism is not strictly explained by the ability to interfere with the synthesis of prostaglandins. The compound is used strictly in local inflammatory diseases (inflammation in the oral and vaginal mucosa). In addition to the therapeutic indications found in the summary of product characteristics (SPC), the compound is used, in high doses, as a psychotropic substance for oral administration, having similar properties to lysergic acid diethylamide (LSD). As an over-the-counter (OTC) compound, it is easy to obtain, and the consequences of using it for purposes other than those assumed by the manufacturer raise various concerns. The reasons are related to the pharmacodynamic and pharmaco-toxicological properties, since neither the mechanism of action nor the possible side effects that would result from systemic consumption, in high doses, even occasionally, have been fully elucidated. The present review aims to analyze the pharmacodynamic properties of benzydamine, starting from the chemical structure, by comparison with structurally similar compounds registered in therapy (as an anti-inflammatory or analgesic) or used for recreational purposes.
Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives
Authors: Petito Giuseppe , Cioffi Federica , Magnacca Nunzia , de Lange Pieter , Senese Rosalba , Lanni Antonia
Published: April 2023

Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3′,5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as “browning”. Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance.
Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
Authors: Xu Nuo , Wong Megan , Balistreri Gabrielle , Nance Elizabeth
Published: April 2023

The development of therapeutics for pediatric use has advanced in the last few decades, yet the off-label use of adult medications in pediatrics remains a significant clinical problem. Nano-based medicines are important drug delivery systems that can improve the bioavailability of a range of therapeutics. However, the use of nano-based medicines for application in pediatric populations is challenged by the lack of pharmacokinetic (PK) data in this population. To address this data gap, we investigated the PK of polymer-based nanoparticles in term-equivalent neonatal rats. We used poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles, which are polymer nanoparticles that have been extensively studied in adult populations but less commonly applied in neonates and pediatrics. We quantified the PK parameters and biodistribution of PLGA-PEG nanoparticles in term-equivalent healthy rats and revealed the PK and biodistribution of polymeric nanoparticles in neonatal rats. We further explored the effects of surfactant used to stabilize PLGA-PEG particles on PK and biodistribution. We showed that 4 h post intraperitoneal injection, nanoparticles had the highest accumulation in serum, at 54.0% of the injected dose for particles with Pluronic® F127 (F127) as the stabilizer and at 54.6% of the injected dose for particles with Poloxamer 188 (P80) as the stabilizer. The half-life of the F127-formulated PLGA-PEG particles was 5.9 h, which was significantly longer than the 1.7 h half-life of P80-formulated PLGA-PEG particles. Among all organs, the liver had the highest nanoparticle accumulation. At 24 h after administration, the accumulation of F127-formulated PLGA-PEG particles was at 26.2% of the injected dose, and the accumulation of P80-formulated particles was at 24.1% of the injected dose. Less than 1% of the injected nanoparticles was observed in healthy rat brain for both F127- and P80-formulated particles. These PK data inform the use of polymer nanoparticle applications in the neonate and provide a foundation for the translation of polymer nanoparticles for drug delivery in pediatric populations.
Metal and Metal Oxides Nanoparticles and Nanosystems in Anticancer and Antiviral Theragnostic Agents
Authors: Shabatina Tatyana I. , Vernaya Olga I. , Shimanovskiy Nikolay L. , Melnikov Mikhail Ya.
Published: April 2023

The development of antiviral treatment and anticancer theragnostic agents in recent decades has been associated with nanotechnologies, and primarily with inorganic nanoparticles (INPs) of metal and metal oxides. The large specific surface area and its high activity make it easy to functionalize INPs with various coatings (to increase their stability and reduce toxicity), specific agents (allowing retention of INPs in the affected organ or tissue), and drug molecules (for antitumor and antiviral therapy). The ability of magnetic nanoparticles (MNPs) of iron oxides and ferrites to enhance proton relaxation in specific tissues and serve as magnetic resonance imaging contrast agents is one of the most promising applications of nanomedicine. Activation of MNPs during hyperthermia by an external alternating magnetic field is a promising method for targeted cancer therapy. As therapeutic tools, INPs are promising carriers for targeted delivery of pharmaceuticals (either anticancer or antiviral) via magnetic drug targeting (in case of MNPs), passive or active (by attaching high affinity ligands) targeting. The plasmonic properties of Au nanoparticles (NPs) and their application for plasmonic photothermal and photodynamic therapies have been extensively explored recently in tumor treatment. The Ag NPs alone and in combination with antiviral medicines reveal new possibilities in antiviral therapy. The prospects and possibilities of INPs in relation to magnetic hyperthermia, plasmonic photothermal and photodynamic therapies, magnetic resonance imaging, targeted delivery in the framework of antitumor theragnostic and antiviral therapy are presented in this review.
Recent Advances in Mitochondrial Fission/Fusion-Targeted Therapy in Doxorubicin-Induced Cardiotoxicity
Authors: Maneechote Chayodom , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: April 2023

Doxorubicin (DOX) has been recognized as one of the most effective chemotherapies and extensively used in the clinical settings of human cancer. However, DOX-mediated cardiotoxicity is known to compromise the clinical effectiveness of chemotherapy, resulting in cardiomyopathy and heart failure. Recently, accumulation of dysfunctional mitochondria via alteration of the mitochondrial fission/fusion dynamic processes has been identified as a potential mechanism underlying DOX cardiotoxicity. DOX-induced excessive fission in conjunction with impaired fusion could severely promote mitochondrial fragmentation and cardiomyocyte death, while modulation of mitochondrial dynamic proteins using either fission inhibitors (e.g., Mdivi-1) or fusion promoters (e.g., M1) can provide cardioprotection against DOX-induced cardiotoxicity. In this review, we focus particularly on the roles of mitochondrial dynamic pathways and the current advanced therapies in mitochondrial dynamics-targeted anti-cardiotoxicity of DOX. This review summarizes all the novel insights into the development of anti-cardiotoxic effects of DOX via the targeting of mitochondrial dynamic pathways, thereby encouraging and guiding future clinical investigations to focus on the potential application of mitochondrial dynamic modulators in the setting of DOX-induced cardiotoxicity.
Strategies for Improving Transdermal Administration: New Approaches to Controlled Drug Release
Authors: Dumitriu Buzia Olimpia , Păduraru Ana Maria , Stefan Claudia Simona , Dinu Monica , Cocoș Dorin Ioan , Nwabudike Lawrence Chukwudi , Tatu Alin Laurențiu
Published: April 2023

In this work, we aim to address several strategies to improve transdermal drug delivery, such as iontophoresis, sonophoresis, electroporation and micron. We also propose a review of some transdermal patches and their applications in medicine. TDDs (transdermal patches with delayed active substances) are multilayered pharmaceutical preparations that may contain one or more active substances, of which, systemic absorption is achieved through intact skin. The paper also presents new approaches to the controlled release of drugs: niosomes, microemulsions, transfersomes, ethosomes, but also hybrid approaches nanoemulsions and microns. The novelty of this review lies in the presentation of strategies to improve the transdermal administration of drugs, combined with their applications in medicine, in light of pharmaceutical technological developments.
Key Design Features of Lipid Nanoparticles and Electrostatic Charge-Based Lipid Nanoparticle Targeting
Authors: Gyanani Vijay , Goswami Roshan
Published: April 2023

Lipid nanoparticles (LNP) have gained much attention after the approval of mRNA COVID-19 vaccines. The considerable number of currently ongoing clinical studies are testament to this fact. These efforts towards the development of LNPs warrant an insight into the fundamental developmental aspects of such systems. In this review, we discuss the key design aspects that confer efficacy to a LNP delivery system, i.e., potency, biodegradability, and immunogenicity. We also cover the underlying considerations regarding the route of administration and targeting of LNPs to hepatic and non-hepatic targets. Furthermore, since LNP efficacy is also a function of drug/nucleic acid release within endosomes, we take a holistic view of charged-based targeting approaches of LNPs not only in the context of endosomal escape but also in relation to other comparable target cell internalization strategies. Electrostatic charge-based interactions have been used in the past as a potential strategy to enhance the drug release from pH-sensitive liposomes. In this review, we cover such strategies around endosomal escape and cell internalization in low pH tumor micro-environments.
Pharmacokinetic/Pharmacodynamic Analysis of Oral Calcium Fosfomycin: Are Urine Levels Sufficient to Ensure Efficacy for Urinary Tract Infections?
Authors: Rodríguez-Gascón Alicia , Alarcia-Lacalle Ana , Solinís María Ángeles , del Pozo-Rodríguez Ana , Abajo Zuriñe , Cabero María , Canut Andrés , Isla Arantxa
Published: April 2023

Urinary tract infections (UTIs) are extremely common and a major driver for the use of antimicrobials. Calcium fosfomycin is an old antibiotic indicated for the treatment of UTIs; however, data about its urine pharmacokinetic profile are scarce. In this work, we have evaluated the pharmacokinetics of fosfomycin from urine concentrations after oral administration of calcium fosfomycin to healthy women. Moreover, we have assessed, by pharmacokinetic/pharmacodynamic (PK/PD) analysis and Monte Carlo simulations, its effectiveness considering the susceptibility profile of Escherichia coli, the main pathogen involved in UTIs. The accumulated fraction of fosfomycin excreted in urine was around 18%, consistent with its low oral bioavailability and its almost exclusively renal clearance by glomerular filtration as unchanged drug. PK/PD breakpoints resulted to be 8, 16, and 32 mg/L for a single dose of 500 mg, a single dose of 1000 mg, and 1000 mg q8h for 3 days, respectively. For empiric treatment, the estimated probability of treatment success was very high (>95%) with the three dose regimens, considering the susceptibility profile of E. coli reported by EUCAST. Our results show that oral calcium fosfomycin at a dose level of 1000 mg every 8 h provides urine concentrations sufficient to ensure efficacy for the treatment of UTIs in women.
Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
Authors: Fuster Marta G. , Montalbán Mercedes G. , Moulefera Imane , Víllora Gloria , Kaplan David L.
Published: April 2023

The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton’s tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages and plays a crucial role in the tumor microenvironment. However, clinical trials with the drug have resulted in conflicting outcomes against solid tumors. In this study, folic acid-conjugated silk nanoparticles were used for the targeted delivery of IB to the cancer cell lines HeLa, BT-474, and SKBR3 by exploiting the overexpression of folate receptors on their surfaces. The results were compared with those of control healthy cells (EA.hy926). Cellular uptake studies confirmed total internalization of the nanoparticles functionalized by this procedure in the cancer cells after 24 h, compared to nanoparticles not functionalized with folic acid, suggesting that cellular uptake was mediated by folate receptors overexpressed in the cancer cells. The results indicate that the developed nanocarrier can be used for drug targeting applications by enhancing IB uptake in cancer cells with folate receptor overexpression.
An Overview of Nanoemulgels for Bioavailability Enhancement in Inflammatory Conditions via Topical Delivery
Authors: Lal Diwya Kumar , Kumar Bhavna , Saeedan Abdulaziz S. , Ansari Mohd Nazam
Published: April 2023

The anti-inflammatory drugs that are generally available possess the disadvantage of hydrophobicity, which leads to poor permeability and erratic bioavailability. Nanoemulgels (NEGs) are novel drug delivery systems that aim to improve the solubility and permeability of drugs across the biological membrane. The nano-sized droplets in the nanoemulsion enhance the permeation of the formulation, along with surfactants and co-surfactants that act as permeation enhancers and can further improve permeability. The hydrogel component of NEG helps to increase the viscosity and spreadability of the formulation, making it ideal for topical application. Moreover, oils that have anti-inflammatory properties, such as eucalyptus oil, emu oil and clove oil, are used as oil phases in the preparation of the nanoemulsion, which shows a synergistic effect with active moiety and enhances its overall therapeutic profile. This leads to the creation of hydrophobic drugs that possess enhanced pharmacokinetic and pharmacodynamic properties, and simultaneously avoid systemic side effects in individuals with external inflammatory disorders. The nanoemulsion’s effective spreadability, ease of application, non-invasive administration, and subsequent ability to achieve patient compliance make it more suitable for topical application in the combat of many inflammatory disorders, such as dermatitis, psoriasis, rheumatoid arthritis, osteoarthritis and so on. Although the large-scale practical application of NEG is limited due to problems regarding its scalability and thermodynamic instability, which arise from the use of high-energy approaches during the production of the nanoemulsion, these can be resolved by the advancement of an alternative nanoemulsification technique. Considering the potential advantages and long-term benefits of NEGs, the authors of this paper have compiled a review that elaborates the potential significance of utilizing nanoemulgels in a topical delivery system for anti-inflammatory drugs.
Strategies to Enhance Drug Permeability across Biological Barriers—A Summary of This Important Special Issue
Authors: Wen Jingyuan , Huang Yuan
Published: April 2023

This Special Issue, “Strategies to Enhance Drug Permeability across Biological Barriers”, is hosted by Pharmaceutics and highlights the recent technological advancements for overcoming biological barriers and improving drug permeability and absorption [...]
HER2/neu Oncogene Silencing in a Breast Cancer Cell Model Using Cationic Lipid-Based Delivery Systems
Authors: Balgobind Adhika , Daniels Aliscia , Ariatti Mario , Singh Moganavelli
Published: April 2023

The overexpression of the human epidermal growth factor 2 (HER2/neu) oncogene is predictive of adverse breast cancer prognosis. Silencing the HER2/neu overexpression using siRNA may be an effective treatment strategy. Major requirements for siRNA-based therapy are safe, stable, and efficient delivery systems to channel siRNA into target cells. This study assessed the efficacy of cationic lipid-based systems for the delivery of siRNA. Cationic liposomes were formulated with equimolar ratios of the respective cholesteryl cytofectins, 3β-N-(N′, N′-dimethylaminopropyl)-carbamoyl cholesterol (Chol-T) or N, N-dimethylaminopropylaminylsuccinylcholesterylformylhydrazide (MS09), with the neutral helper lipid, dioleoylphosphatidylethanolamine (DOPE), with and without a polyethylene glycol stabilizer. All cationic liposomes efficiently bound, compacted, and protected the therapeutic siRNA against nuclease degradation. Liposomes and siRNA lipoplexes were spherical, <200 nm in size, with moderate particle size distributions (PDI < 0.4). The siRNA lipoplexes exhibited minimal dose-dependent cytotoxicity and effective HER2/neu siRNA transfection in the HER2/neu overexpressing SKBR-3 cells. The non-PEGylated Chol-T-siRNA lipoplexes induced the highest HER2/neu silencing at the mRNA (10000-fold decrease) and protein levels (>111.6-fold decrease), surpassing that of commercially available Lipofectamine 3000 (4.1-fold reduction in mRNA expression). These cationic liposomes are suitable carriers of HER2/neu siRNA for gene silencing in breast cancer.
Smart Poly(lactide)-b-poly(triethylene glycol methyl ether methacrylate) (PLA-b-PTEGMA) Block Copolymers: One-Pot Synthesis, Temperature Behavior, and Controlled Release of Paclitaxel
Authors: Lukáš Petrova Svetlana , Vragović Martina , Pavlova Ewa , Černochová Zulfiya , Jäger Alessandro , Jäger Eliézer , Konefał Rafał
Published: April 2023

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.