bluuebunny/crossref_metadata_2025 huggingface dataset:
Macronutrients Intake and Risk of Stomach Cancer: Findings from Case-Control Study
Authors: Allehdan Sabika , Bassil Maya , Alatrash Razan M. , Al-Jaberi Tareq , Hushki Ahmad , Rayyan Yaser , Dahoud Mahammad , Abu-EIteen Khaled , Tayyem Reema F.
Published: June 2022

Studies on the association between gastric cancer (GC) and the intake of nutrients in Jordan are very limited, while findings from other reports on the intake of energy and macronutrients are controversial. This study aimed to examine the associations between intake of energy and macronutrients and the risk of GC in a Jordanian population. A case-control study was carried out between March 2015 and August 2018 in four major hospitals, including an oncology center in Jordan. Study participants were 173 cases with incident and histologically confirmed GC and 314 frequency-matched controls. Interview-based questionnaires were used to obtain the study’s information. Data on nutrient intake were collected using a validated Arabic food-frequency questionnaire (FFQ). Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated through multinomial logistic regression and adjusted for potential confounders, including age, marital status, education, body mass index (BMI), smoking, period of smoking, family history of gastric cancer, history of gastric ulcer, and physical activity. Intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, trans-fat, and omega-6 fatty acids were significantly associated with increased risk of GC. The ORs for the highest versus the lowest tertiles were 6.47 (95% Cl: 3.29–12.77), 2.97 (95% CI: 1.58–5.58), 6.84 (95% CI: 3.46–13.52), 6.19 (95% CI: 3.15–12.17), 3.05 (95% CI: 1.58–5.88), 8.11 (95% CI: 4.20–15.69), and 2.74 (95% CI: 1.47–5.09), respectively. No significant association was found for energy, protein, carbohydrate, sugar, fibers, and omega-3 fatty acids. The findings of this study suggest that high intake of selected types of fats was associated with an increased risk of GC.
Personalized Nutrition Using Microbial Metabolite Phenotype to Stratify Participants and Non-Invasive Host Exfoliomics Reveal the Effects of Flaxseed Lignan Supplementation in a Placebo-Controlled Crossover Trial
Authors: Mullens Destiny A. , Ivanov Ivan , Hullar Meredith A. J. , Randolph Timothy W. , Lampe Johanna W. , Chapkin Robert S.
Published: June 2022

High-fiber plant foods contain lignans that are converted to bioactive enterolignans, enterolactone (ENL) and enterodiol (END) by gut bacteria. Previously, we conducted an intervention study to gain mechanistic insight into the potential chemoprotective effects of flaxseed lignan supplementation (secoisolariciresinol diglucoside; SDG) compared to a placebo in 42 men and women. Here, we expand on these analyses to further probe the impact of the microbial metabolite phenotype on host gene expression in response to lignan exposure. We defined metabolic phenotypes as high- or low-ENL excretion based on the microbial metabolism of SDG. RNA-seq was used to assess host gene expression in fecal exfoliated cells. Stratified by microbial ENL excretion, differentially expressed (DE) genes in high- and low-ENL excreter groups were compared. Linear discriminant analysis using the ENL phenotypes identified putative biomarker combinations of genes capable of discriminating the lignan treatment from the placebo. Following lignan intervention, a total of 165 DE genes in high-ENL excreters and 1450 DE genes in low-ENL excreters were detected. Functional analysis identified four common upstream regulators (master genes): CD3, IFNG, IGF1 and TNFRSF1A. Our findings suggest that the enhanced conversion of flaxseed lignan to ENL is associated with a suppressed inflammatory status.
Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy
Authors: Aaseth Jan O. , Rootwelt Helge , Retterstøl Kjetil , Hestad Knut , Farup Per G.
Published: June 2022

The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs.
Factors Associated with Food Insecurity among Pregnant Women and Caregivers of Children Aged 0–6 Years: A Scoping Review
Authors: Bastian Amber , Parks Courtney , Yaroch Amy , McKay Fiona H. , Stern Katie , van der Pligt Paige , McNaughton Sarah A. , Lindberg Rebecca
Published: June 2022

With a global focus on improving maternal and child nutrition through the 2030 Sustainable Development Goals, it is important to understand food insecurity in pregnant women and families with young children, as food insecurity at these life stages can have ongoing negative health consequences. However, factors that influence food insecurity among this population group are not well understood. This scoping review investigates the factors that influence food insecurity among pregnant women and households with young children aged 0–6 years living in high-income countries. A scoping literature review was conducted using four electronic databases. The search combined terms relevant to: food security, determinants, pregnancy and family and high-income countries. Only full text and English language articles were included. The search identified 657 titles and abstracts; 29 articles were included in the review. A majority (70%) of the studies were conducted in the United States and were mostly either cross-sectional or secondary data analysis of existing population data. Factors associated with food insecurity were identified and grouped into 13 constructs. These included social, economic and health risk factors, food access and utilization factors and health and dietary outcomes. This scoping review identifies the factors associated with food insecurity among pregnant women and families with young children that could be used to better measure and understand food insecurity, which could assist in developing program and policy responses. This review also highlights the lack of literature from high-income countries outside the US.
Association of Dietary Inflammatory Potential with Blood Inflammation: The Prospective Markers on Mild Cognitive Impairment
Authors: Wang Xuan , Li Tiantian , Li Hongrui , Li Dajun , Wang Xianyun , Zhao Ai , Liang Wannian , Xiao Rong , Xi Yuandi
Published: June 2022

Inflammation is known as an important mechanism of cognitive dysfunction. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) are two blood inflammatory markers, which are related to many chronic diseases including cognitive impairment. It is recognized that dietary inflammatory index (DII), which is used to estimate the overall inflammatory potential of diet, may be related to mild cognitive impairment (MCI) as well. This study aimed to explore the relationship between SII, SIRI and DII, as well as the role of these inflammatory indexes on MCI in elderly people. A total of 1050 participants from Beijing were included. Neuropsychological tests were used for cognitive evaluation. Energy-adjusted DII scores were calculated based on semi-quantitative food frequency questionnaire. Blood samples were tested for calculating SII and SIRI. Log-binomial regression models were used to estimate the correlation of indexes. After adjusting demographic characteristics, SII and SIRI in MCI individuals were higher than controls (p ≤ 0.001). DII, SII and SIRI had positive relationship with MoCA scores (p < 0.005). DII also correlated with SIRI in MCI (β = 0.11, p = 0.031). Higher DII and SIRI could definitely increase the risk of MCI, as well as DII and SII (p < 0.005). In conclusion, DII was positively correlated with blood inflammation. The elderly with higher level of DII and SIRI, or DII and SII could be considered as people with higher risk of developing MCI.
Racial and Ethnic Differences in Eating Duration and Meal Timing: Findings from NHANES 2011–2018
Authors: Ansu Baidoo Velarie Y. , Zee Phyllis C. , Knutson Kristen L.
Published: June 2022

Background: In addition to quantity and quality, meal timing and eating duration are additional dietary characteristics that impact cardiometabolic health. Given that cardiometabolic health disparities exist among racial and ethnic groups, we examined whether meal timing and eating duration are additional diet-related differences among racial and ethnic groups. Methods: Participants (n = 13,084) were adults (≥20 years) from the National Health and Nutrition Examination (NHANES, 2011–2018) Survey. Times of first and last meal and the interval between them (eating duration) were derived from two 24-h dietary recalls. Multiple linear regression analyses compared these variables among race and ethnicity after adjusting for potential confounders. Results: Compared to non-Hispanic White adults, the first mealtime was significantly later for Mexican American (23 min), Non-Hispanic Asian (15 min), Non-Hispanic Black (46 min), and Other Hispanic (20 min) and Other Racial (14 min) adults (all p < 0.05). Mexican American and Non-Hispanic Asian adults had a significantly different last mealtime by 13 min earlier and 25 min later, respectively, compared to Non-Hispanic White adults. Compared to Non-Hispanic White adults, the mean eating duration was shorter for other Hispanic (20 min), Mexican American (36 min), and Non-Hispanic Black (49 min) adults. Conclusions: Meal timing and eating duration are additional dietary characteristics that vary significantly among racial and ethnic groups.
Comment on Kremer et al. Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies. Nutrients 2021, 13, 3069
Authors: Janssen Rob , Walk Jona , Vermeer Cees
Published: June 2022

In the article “Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies”, Kremer et al. [...]
Combination of Photodynamic Therapy and Oral Antifungals for the Treatment of Onychomycosis
Authors: Navarro-Bielsa Alba , Gracia-Cazaña Tamara , Robres Pilar , Lopez Concepción , Calvo-Priego María Dolores , Aspiroz Carmen , Gilaberte Yolanda
Published: June 2022

Onychomycosis accounts for 50% of nail disorders, making it one of the most prevalent fungal diseases and a therapeutic challenge. Photodynamic therapy (PDT) could constitute a therapeutic alternative, owing to its good adherence, the low probability of resistance, the lack of interaction with antimicrobials, and its favorable adverse effect profile. This retrospective observational study included all patients with a microbiological diagnosis of onychomycosis treated with PDT at Miguel Servet University Hospital, Zaragoza (Spain), between January 2013 and June 2021. The protocol consisted of pre-treatment with 40% urea for 7 days, followed by 16% methyl-aminolevulinate (MAL) for 3 h and subsequent irradiation with a red-light LED lamp (37 J/cm2), every 1 or 2 weeks. Combined treatment with oral and/or topical antifungals was recorded. Of the 20 patients included (mean age, 59 ± 17 years), 55% were men. The most frequently detected microorganism was Trichophyton rubrum (55%). The most commonly affected location was the feet (90%): 50% of these cases were associated with tinea pedis. The median (standard deviation) number of PDT sessions was 6 (2.8). PDT was combined with systemic terbinafine (250 mg/day) in 10 cases (in 8 cases, this was administered for only 1 month), and with topical terbinafine in 3 cases. A complete clinical response was achieved in 80% (16) of cases and microbiological cure in 60% (12). PDT is a therapeutic alternative for onychomycosis, and can be administered either in monotherapy or combined with antifungals, allowing for a reduction in the duration and possible adverse effects of antifungal treatment and achieving higher cure rates than those obtained with either treatment alone.
Purification, Characterization and Evaluation of the Antitumoral Activity of a Phospholipase A2 from the Snake Bothrops moojeni
Authors: Frihling Breno Emanuel Farias , Boleti Ana Paula de Araújo , de Oliveira Caio Fernando Ramalho , Sanches Simone Camargo , Cardoso Pedro Henrique de Oliveira , Verbisck Newton , Macedo Maria Lígia Rodrigues , Rita Paula Helena Santa , Carvalho Cristiano Marcelo Espinola , Migliolo Ludovico
Published: June 2022

Nature presents a wide range of biomolecules with pharmacological potential, including venomous animal proteins. Among the protein components from snake venoms, phospholipases (PLA2) are of great importance for the development of new anticancer compounds. Thus, we aimed to evaluate the PLA2 anticancer properties from Bothrops moojeni venom. The crude venom was purified through three chromatographic steps, monitored by enzymatic activity and SDS-PAGE (12%). The purified PLA2 denominated BmPLA2 had its molecular mass and N-terminal sequence identified by mass spectrometry and Edman degradation, respectively. BmPLA2 was assayed against human epithelial colorectal adenocarcinoma cells (Caco-2), human rhabdomyosarcoma cells (RD) and mucoepidermoid carcinoma of the lung (NCI-H292), using human fibroblast cells (MRC-5) and microglia cells (BV-2) as a cytotoxicity control. BmPLA2 presented 13,836 Da and a 24 amino acid-residue homologue with snake PLA2, which showed a 90% similarity with other Bothrops moojeni PLA2. BmPLA2 displayed an IC50 of 0.6 µM against Caco-2, and demonstrated a selectivity index of 1.85 (compared to MRC-5) and 6.33 (compared to BV-2), supporting its selectivity for cancer cells. In conclusion, we describe a new acidic phospholipase, which showed antitumor activity and is a potential candidate in the development of new biotechnological tools.
[6]-Shogaol Attenuates Oxaliplatin-Induced Allodynia through Serotonergic Receptors and GABA in the Spinal Cord in Mice
Authors: Kim Suyong , Gang Juan , Lee Ji-Hwan , Yang Hyejin , Cheon Chunhoo , Ko Seong-Gyu , Bae Hyunsu , Kim Woojin
Published: June 2022

Although oxaliplatin is a well-known anti-cancer agent used for the treatment of colorectal cancer, treated patients often experience acute cold and mechanical allodynia as side effects. Unfortunately, no optimal treatment has been developed yet. In this study, [6]-shogaol (10 mg/kg, i.p.), which is one of the major bioactive components of Zingiber officinale roscoe (Z. officinale), significantly alleviated allodynia induced by oxaliplatin (6 mg/kg, i.p.) injection. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. The analgesic effect of [6]-shogaol was blocked by the intrathecal injection of 5-HT1A, 5-HT3, and GABAB receptor antagonists, NAN-190 (1 μg), MDL-72222 (15 μg), and CGP 55845 (10 μg), respectively. Furthermore, oxaliplatin injection lowered the GABA concentration in the superficial laminae of the spinal dorsal horn, whereas [6]-shogaol injection significantly elevated it. The GAD (glutamic acid decarboxylase) 65 concentration also increased after [6]-shogaol administration. However, pre-treatment of NAN-190 completely inhibited the increased GABA induced by [6]-shogaol in the spinal dorsal horn, whereas MDL-72222 partially blocked the effect. Altogether, these results suggest that [6]-shogaol could attenuate oxaliplatin-induced cold and mechanical allodynia through 5-HT1A and 5-HT3 receptor antagonists located in the GABAergic neurons in the spinal dorsal horn in mice.
Sesamol Loaded Albumin Nanoparticles: A Boosted Protective Property in Animal Models of Oxidative Stress
Authors: Zaher Sara , Soliman Mahmoud E. , Elsabahy Mahmoud , Hathout Rania M.
Published: June 2022

The current study evaluated the ability of sesamol-loaded albumin nanoparticles to impart protection against oxidative stress induced by anthracyclines in comparison to the free drug. Albumin nanoparticles were prepared via the desolvation technique and then freeze-dried with the cryoprotectant, trehalose. Albumin concentration, pH, and type of desolvating agent were assessed as determining factors for successful albumin nanoparticle fabrication. The optimal nanoparticles were spherical in shape, and they had an average particle diameter of 127.24 ± 2.12 nm with a sesamol payload of 96.89 ± 2.4 μg/mg. The drug cellular protection was tested on rat hepatocytes pretreated with 1 µM doxorubicin, which showed a 1.2-fold higher protective activity than the free sesamol. In a pharmacokinetic study, the loading of a drug onto nanoparticles resulted in a longer half-life and mean residence time, as compared to the free drug. Furthermore, in vivo efficacy and biochemical assessment of lipid peroxidation, cardiac biomarkers, and liver enzymes were significantly ameliorated after administration of the sesamol-loaded albumin nanoparticles. The biochemical assessments were also corroborated with the histopathological examination data. Sesamol-loaded albumin nanoparticles, prepared under controlled conditions, may provide an enhanced protective effect against off-target doxorubicin toxicity.
Promising Therapeutic Strategies for Colorectal Cancer Treatment Based on Nanomaterials
Authors: Krasteva Natalia , Georgieva Milena
Published: June 2022

Colorectal cancer (CRC) is a global health problem responsible for 10% of all cancer incidences and 9.4% of all cancer deaths worldwide. The number of new cases increases per annum, whereas the lack of effective therapies highlights the need for novel therapeutic approaches. Conventional treatment methods, such as surgery, chemotherapy and radiotherapy, are widely applied in oncology practice. Their therapeutic success is little, and therefore, the search for novel technologies is ongoing. Many efforts have focused recently on the development of safe and efficient cancer nanomedicines. Nanoparticles are among them. They are uniquewith their properties on a nanoscale and hold the potential to exploit intrinsic metabolic differences between cancer and healthy cells. This feature allows them to induce high levels of toxicity in cancer cells with little damage to the surrounding healthy tissues. Graphene oxide is a promising 2D material found to play an important role in cancer treatments through several strategies: direct killing and chemosensitization, drug and gene delivery, and phototherapy. Several new treatment approaches based on nanoparticles, particularly graphene oxide, are currently under research in clinical trials, and some have already been approved. Here, we provide an update on the recent advances in nanomaterials-based CRC-targeted therapy, with special attention to graphene oxide nanomaterials. We summarise the epidemiology, carcinogenesis, stages of the CRCs, and current nanomaterials-based therapeutic approaches for its treatment.
Liposomal β-Sitosterol Suppresses Metastasis of CT26/luc Colon Carcinoma via Inhibition of MMP-9 and Evoke of Immune System
Authors: Shen Chao-Yu , Lee Chia-Fen , Chou Wei-Taur , Hwang Jeng-Jong , Tyan Yeu-Sheng , Chuang Hui-Yen
Published: June 2022

β-sitosterol (SITO) has been reported with anticancer effects; however, with poor bioavailability. The current study aimed to investigate whether liposomal encapsulated β-sitosterol (LS) has a better inhibition effect on tumor metastasis than β-sitosterol in a CT26/luc lung metastasis mouse model and the possible underlying mechanism. LS was liposomal-encapsulated SITO and was delivered to mice by oral gavage. The cell viability was determined by the MTT assay, and invasiveness of the tumor cells and related protein expression were evaluated with the invasion assay and Western blotting. For therapeutic efficacy evaluation, male BALB/c mice were treated with PBS, SITO, and LS once a day for 7 days prior to intravenous injections of CT26/luc cells; treatments were continued twice a week post-cell inoculation throughout the entire experiment. Tumor growth inhibition was monitored by bioluminescent imaging (BLI). IL-12, IL-18, and IFN-γ in the intestinal epithelium were determined by ELISA. The results show that LS treatment had a better invasion inhibition with lower cytotoxicity than SITO when the same dose was utilized. Notably, mice treated with LS significantly exhibited fewer metastases to the lungs and other tissues/organs compared with the Control and SITO groups. Additionally, the IL-12, IL-18, and IFN-γ levels were significantly increased in the LS-treated mice compared with the Control and SITO groups. The underlying mechanism may be through the inhibition of MMP-9 and elicitation of the antitumoral Th1 immune response, such as increasing CD4+ and CD8+ T cells, IL-12, IL-18, and IFN-γ.
Relevance of Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in Routine Clinical Practice: A Pilot Study
Authors: Escudero-Ortiz Vanesa , Domínguez-Leñero Vanessa , Catalán-Latorre Ana , Rebollo-Liceaga Joseba , Sureda Manuel
Published: June 2022

Introduction: The main goal of treatment in cancer patients is to achieve the highest therapeutic effectiveness with the least iatrogenic toxicity. Tyrosine kinase inhibitors (TKIs) are anticancer oral agents, usually administered at fixed doses, which present high inter- and intra-individual variability due to their pharmacokinetic characteristics. Therapeutic drug monitoring (TDM) can be used to optimize the use of several types of medication. Objective: We evaluated the use of TDM of TKIs in routine clinical practice through studying the variability in exposure to erlotinib, imatinib, lapatinib, and sorafenib and dose adjustment. Materials and methods: We conducted a retrospective analytical study involving patients who received treatment with TKIs, guided by TDM and with subsequent recommendation of dose adjustment. The quantification of the plasma levels of the different drugs was performed using high-performance liquid chromatography (HPLC). The Clinical Research Ethics Committee of the Hospital Quirónsalud Torrevieja approved this study. Results: The inter-individual variability in the first cycle and in the last monitored cycle was 46.2% and 44.0% for erlotinib, 48.9 and 50.8% for imatinib, 60.7% and 56.0% for lapatinib and 89.7% and 72.5% for sorafenib. Relationships between exposure and baseline characteristics for erlotinib, imatinib, lapatinib and sorafenib were not statistically significant for any of the variables evaluated (weight, height, body surface area (BSA), age and sex). Relationships between height (p = 0.021) and BSA (p = 0.022) were statistically significant for sorafenib. No significant relationships were observed between Ctrough and progression-free survival (PFS) or overall survival (OS) for any drug, except in the case of sunitinib (correlation between Ctrough and PFS p = 0.023) in the exposure–efficacy analysis. Conclusions: Erlotinib, imatinib, lapatinib and sorafenib show large inter-individual variability in exposure. TDM entails a significant improvement in exposure and enables more effective and safe use of TKIs in routine clinical practice.
Surface-Functionalized NdVO4:Gd3+ Nanoplates as Active Agents for Near-Infrared-Light-Triggered and Multimodal-Imaging-Guided Photothermal Therapy
Authors: Deng Kerong , Liu Donglian , Wang Ziyan , Zhou Zhaoru , Chen Qianyi , Luo Jiamin , Zhang Yaru , Hou Zhiyao , Lin Jun
Published: June 2022

Development of nanotheranostic agents with near-infrared (NIR) absorption offers an effective tool for fighting malignant diseases. Lanthanide ion neodymium (Nd3+)-based nanomaterials, due to the maximum absorption at around 800 nm and unique optical properties, have caught great attention as potential agents for simultaneous cancer diagnosis and therapy. Herein, we employed an active nanoplatform based on gadolinium-ion-doped NdVO4 nanoplates (NdVO4:Gd3+ NPs) for multiple-imaging-assisted photothermal therapy. These NPs exhibited enhanced NIR absorption and excellent biocompatibility after being grafted with polydopamine (pDA) and bovine serum albumin (BSA) layers on their surface. Upon expose to an 808 nm laser, these resulting NPs were able to trigger hyperthermia rapidly and cause photo-destruction of cancer cells. In a xenograft tumor model, tumor growth was also significantly inhibited by these photothermal agents under NIR laser irradiation. Owing to the multicomponent nanostructures, we demonstrated these nanoagents as being novel contrast agents for in vivo magnetic resonance (MR) imaging, X-ray computed tomography (CT), photoacoustic (PA) imaging, and second biological window fluorescent imaging of tumor models. Thus, we believe that this new kind of nanotherapeutic will benefit the development of emerging nanosystems for biological imaging and cancer therapy.
pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation
Authors: Aslam Mariam , Barkat Kashif , Malik Nadia Shamshad , Alqahtani Mohammed S. , Anjum Irfan , Khalid Ikrima , Tulain Ume Ruqia , Gohar Nitasha , Zafar Hajra , Paiva-Santos Ana Cláudia , Raza Faisal
Published: June 2022

The objective of this study was to fabricate and evaluate a pH sensitive cross-linked polymeric network through the free radical polymerization technique for the model drug, cyclophosphamide, used in the treatment of non-Hodgkin’s lymphoma. The Hydrogels were prepared using a polymeric blend of agarose, Pluronic acid, glutaraldehyde, and methacrylic acid. The prepared hydrogels were characterized for drug loading (%), swelling pattern, release behavior, the ingredient’s compatibility, structural evaluation, thermal integrity, and toxicity evaluation in rabbits. The new polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 58.65–75.32%. The developed hydrogels showed significant differences in swelling dynamics and drug release behavior in simulated intestinal fluid (SIF) when compared with simulated gastric fluid (SGF). The drug release was persistent and performed in a controlled manner for up to 24 h. A toxicity study was conducted on white albino rabbits. The developed hydrogels did not show any signs of ocular, skin, or oral toxicity; therefore, these hydrogels can be regarded as safe and potential carriers for controlled drug delivery in biomedical applications.
Development of Nafamostat Mesylate Immediate-Release Tablet by Drug Repositioning Using Quality-by-Design Approach
Authors: Kim Hyeon-A , Kim Joo-Eun
Published: June 2022

We aimed to develop nafamostat mesylate immediate-release tablets for the treatment of COVID-19 through drug repositioning studies of nafamostat mesylate injection. Nafamostat mesylate is a serine protease inhibitor known to inhibit the activity of the transmembrane protease, serine 2 enzyme that affects the penetration of the COVID-19 virus, thereby preventing the binding of the angiotensin-converting enzyme 2 receptor in vivo and the spike protein of the COVID-19 virus. The formulation was selected through a stability study after manufacturing by a wet granulation process and a direct tableting process to develop a stable nafamostat mesylate immediate-release tablet. Formulation issues for the selected processes were addressed using the design of experiments and quality-by-design approaches. The dissolution rate of the developed tablet was confirmed to be >90% within 30 min in the four major dissolutions, except in the pH 6.8 dissolution medium. Additionally, an in vivo pharmacokinetic study was performed in monkeys, and the pharmacokinetic profiles of nafamostat injections, oral solutions, and tablets were compared. The half-life during oral administration was confirmed to be significantly longer than the reported literature value of 8 min, and the bioavailability of the tablet was approximately 25% higher than that of the oral solution.
Active Potential of Bacterial Cellulose-Based Wound Dressing: Analysis of Its Potential for Dermal Lesion Treatment
Authors: Hodel Katharine Valéria Saraiva , Machado Bruna Aparecida Souza , Sacramento Giulia da Costa , Maciel Carine Assunção de Oliveira , Oliveira-Junior Gessualdo Seixas , Matos Breno Noronha , Gelfuso Guilherme Martins , Nunes Silmar Baptista , Barbosa Josiane Dantas Viana , Godoy Ana Leonor Pardo Campos
Published: June 2022

The use of innate products for the fast and efficient promotion of healing process has been one of the biomedical sector’s main bets for lesion treatment modernization process. The aim of this study was to develop and characterize bacterial cellulose-based (BC) wound dressings incorporated with green and red propolis extract (2 to 4%) and the active compounds p-coumaric acid and biochanin A (8 to 16 mg). The characterization of the nine developed samples (one control and eight active wound dressings) evidenced that the mechanics, physics, morphological, and barrier properties depended not only on the type of active principle incorporated onto the cellulosic matrix, but also on its concentration. Of note were the results found for transparency (28.59–110.62T600 mm−1), thickness (0.023–0.046 mm), swelling index (48.93–405.55%), water vapor permeability rate (7.86–38.11 g m2 day−1), elongation (99.13–262.39%), and antioxidant capacity (21.23–86.76 μg mL−1). The wound dressing based on BC and red propolis was the only one that presented antimicrobial activity. The permeation and retention test revealed that the wound dressing containing propolis extract presented the most corneal stratum when compared with viable skin. Overall, the developed wound dressing showed potential to be used for treatment against different types of dermal lesions, according to its determined proprieties.
Relation between Plasma Trough Concentration of Pazopanib and Progression-Free Survival in Metastatic Soft Tissue Sarcoma Patients
Authors: Minot-This Marie-Sophie , Boudou-Rouquette Pascaline , Jouinot Anne , de Percin Sixtine , Balakirouchenane David , Khoudour Nihel , Tlemsani Camille , Chauvin Jonathan , Thomas-Schoemann Audrey , Goldwasser François , Blanchet Benoit , Alexandre Jérôme
Published: June 2022

Background: Pazopanib (PAZ) is an oral angiogenesis inhibitor approved to treat soft tissue sarcoma (STS) but associated with a large interpatient pharmacokinetic (PK) variability and narrow therapeutic index. We aimed to define the specific threshold of PAZ trough concentration (Cmin) associated with better progression-free survival (PFS) in STS patients. Methods: In this observational study, PAZ Cmin was monitored over the treatment course. For the primary endpoint, the 3-month PFS in STS was analyzed with logistic regression. Second, we performed exposure–overall survival (OS) (Cox model plus Kaplan–Meier analysis/log-rank test) and exposure–toxicity analyses. Results: Ninety-five STS patients were eligible for pharmacokinetic/pharmacodynamic (PK/PD) assessment. In the multivariable analysis, PAZ Cmin < 27 mg/L was independently associated with a risk of progression at 3 months (odds ratio (OR) 4.21, 95% confidence interval (CI) (1.47–12.12), p = 0.008). A higher average of PAZ Cmin over the first 3 months was associated with a higher risk of grade 3–4 toxicities according to the NCI-CTCAE version 5.0 (OR 1.07 per 1 mg/L increase, CI95 (1.02–1.13), p = 0.007). Conclusion: PAZ Cmin ≥ 27 mg/L was independently associated with improved 3-month PFS in STS patients. Pharmacokinetically-guided dosing could be helpful to optimize the clinical management of STS patients in daily clinical practice.
Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs)
Authors: Huttunen Johanna , Adla Santosh Kumar , Markowicz-Piasecka Magdalena , Huttunen Kristiina M.
Published: June 2022

Membrane transporters have a crucial role in compounds’ brain drug delivery. They allow not only the penetration of a wide variety of different compounds to cross the endothelial cells of the blood–brain barrier (BBB), but also the accumulation of them into the brain parenchymal cells. Solute carriers (SLCs), with nearly 500 family members, are the largest group of membrane transporters. Unfortunately, not all SLCs are fully characterized and used in rational drug design. However, if the structural features for transporter interactions (binding and translocation) are known, a prodrug approach can be utilized to temporarily change the pharmacokinetics and brain delivery properties of almost any compound. In this review, main transporter subtypes that are participating in brain drug disposition or have been used to improve brain drug delivery across the BBB via the prodrug approach, are introduced. Moreover, the ability of selected transporters to be utilized in intrabrain drug delivery is discussed. Thus, this comprehensive review will give insights into the methods, such as computational drug design, that should be utilized more effectively to understand the detailed transport mechanisms. Moreover, factors, such as transporter expression modulation pathways in diseases that should be taken into account in rational (pro)drug development, are considered to achieve successful clinical applications in the future.
Pneumococcal Surface Protein A-Hybrid Nanoparticles Protect Mice from Lethal Challenge after Mucosal Immunization Targeting the Lungs
Authors: Figueiredo Douglas Borges de , Kaneko Kan , Rodrigues Tasson da Costa , MacLoughlin Ronan , Miyaji Eliane Namie , Saleem Imran , Gonçalves Viviane Maimoni
Published: June 2022

Pneumococcal disease remains a global burden, with current conjugated vaccines offering protection against the common serotype strains. However, there are over 100 serotype strains, and serotype replacement is now being observed, which reduces the effectiveness of the current vaccines. Pneumococcal surface protein A (PspA) has been investigated as a candidate for new serotype-independent pneumococcal vaccines, but requires adjuvants and/or delivery systems to improve protection. Polymeric nanoparticles (NPs) are biocompatible and, besides the antigen, can incorporate mucoadhesive and adjuvant substances such as chitosans, which improve antigen presentation at mucosal surfaces. This work aimed to define the optimal NP formulation to deliver PspA into the lungs and protect mice against lethal challenge. We prepared poly(glycerol-adipate-co-ω-pentadecalactone) (PGA-co-PDL) and poly(lactic-co-glycolic acid) (PLGA) NPs using an emulsion/solvent evaporation method, incorporating chitosan hydrochloride (HCl-CS) or carboxymethyl chitosan (CM-CS) as hybrid NPs with encapsulated or adsorbed PspA. We investigated the physicochemical properties of NPs, together with the PspA integrity and biological activity. Furthermore, their ability to activate dendritic cells in vitro was evaluated, followed by mucosal immunization targeting mouse lungs. PGA-co-PDL/HCl-CS (291 nm) or CM-CS (281 nm) NPs produced smaller sizes compared to PLGA/HCl-CS (310 nm) or CM-CS (299 nm) NPs. Moreover, NPs formulated with HCl-CS possessed a positive charge (PGA-co-PDL +17 mV, PLGA + 13 mV) compared to those formulated with CM-CS (PGA-co-PDL −20 mV, PLGA −40 mV). PspA released from NPs formulated with HCl-CS preserved the integrity and biological activity, but CM-CS affected PspA binding to lactoferrin and antibody recognition. PspA adsorbed in PGA-co-PDL/HCl-CS NPs stimulated CD80+ and CD86+ cells, but this was lower compared to when PspA was encapsulated in PLGA/HCl-CS NPs, which also stimulated CD40+ and MHC II (I-A/I-E)+ cells. Despite no differences in IgG being observed between immunized animals, PGA-co-PDL/HCl-CS/adsorbed-PspA protected 83% of mice after lethal pneumococcal challenge, while 100% of mice immunized with PLGA/HCl-CS/encapsulated-PspA were protected. Therefore, this formulation is a promising vaccine strategy, which has beneficial properties for mucosal immunization and could potentially provide serotype-independent protection.
Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis
Authors: Sonoda Hiroyuki , Takahashi Kenichi , Minami Kohtaro , Hirato Toru , Yamamoto Tatsuyoshi , So Sairei , Tanizawa Kazunori , Schmidt Mathias , Sato Yuji
Published: June 2022

Enzyme replacement therapy (ERT) has paved the way for treating the somatic symptoms of lysosomal storage diseases (LSDs), but the inability of intravenously administered enzymes to cross the blood–brain barrier (BBB) has left the central nervous system (CNS)-related symptoms of LSDs largely impervious to the therapeutic benefits of ERT, although ERT via intrathecal and intracerebroventricular routes can be used for some neuronopathic LSDs (in particular, mucopolysaccharidoses). However, the considerable practical issues involved make these routes unsuitable for long-term treatment. Efforts have been made to modify enzymes (e.g., by fusing them with antibodies against innate receptors on the cerebrovascular endothelium) so that they can cross the BBB via receptor-mediated transcytosis (RMT) and address neuronopathy in the CNS. This review summarizes the various scientific and technological challenges of applying RMT to the development of safe and effective enzyme therapeutics for neuronopathic mucopolysaccharidoses; it then discusses the translational and methodological issues surrounding preclinical and clinical evaluation to establish RMT-applied ERT.
Novel Utilization of Therapeutic Coatings Based on Infiltrated Encapsulated Rose Bengal Microspheres in Porous Titanium for Implant Applications
Authors: Accioni Francesca , Rassu Giovanna , Begines Belén , Rodríguez-Albelo Luisa Marleny , Torres Yadir , Alcudia Ana , Gavini Elisabetta
Published: June 2022

Despite the increasing progress achieved in the last 20 years in both the fabrication of porous dental implants and the development of new biopolymers for targeting drug therapy, there are important issues such as bone resorption, poor osseointegration, and bacterial infections that remain as critical challenges to avoid clinical failure problems. In this work, we present a novel microtechnology based on polycaprolactone microspheres that can adhere to porous titanium implant models obtained by the spacer holder technique to allow a custom biomechanical and biofunctional balance. For this purpose, a double emulsion solvent evaporation technique was successfully employed for the fabrication of the microparticles properly loaded with the antibacterial therapeutic agent, rose bengal. The resulting microspheres were infiltrated into porous titanium substrate and sintered at 60 °C for 1 h, obtaining a convenient prophylactic network. In fact, the sintered polymeric microparticles were demonstrated to be key to controlling the drug dissolution rate and favoring the early healing process as consequence of a better wettability of the porous titanium substrate to promote calcium phosphate nucleation. Thus, this joint technology proposes a suitable prophylactic tool to prevent both early-stage infection and late-stage osseointegration problems.
Particle Agglomeration of Acid-Modified Tapioca Starches: Characterization and Use as Direct Compression Fillers in Tablets
Authors: Siriwachirachai Chaipat , Pongjanyakul Thaned
Published: June 2022

Acid-modified tapioca starches (AMTSs) possessed good compressibility but showed poor particle flowability for preparing tablets by the direct compression method. The aims of this work were to prepare and characterize AMTS agglomerates using polyvinylpyrrolidone (PVP) as an agglomerating agent. The dilution potential and stability studies of the AMTS agglomerates were investigated. The results showed that particle enlargement of TS and AMTS could be achieved via agglomeration using PVP. The thermal behavior and molecular interaction of the agglomerates were revealed using DSC and FTIR spectroscopy, respectively. An increase in PVP concentrations resulted in greater particle strength of the TS agglomerates and a higher acid concentration for modification enhanced the strength of the AMTS agglomerates. All agglomerates presented good particle flowability. Moreover, the AMTS agglomerates provided higher compressibility hardness than the TS agglomerates. The addition of PVP could extend the disintegration time and slow drug dissolution from the agglomerate tablets. The humidity of the storage conditions influenced the thickness and hardness of the AMTS agglomerate tablets, and good physical and chemical stability of the tablets was obtained under ambient conditions and in the refrigerator. Furthermore, the AMTS agglomerates displayed good carrying capacity and possessed desirable characteristics for use in direct compression tablets.
CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease
Authors: Rahman Mujeeb ur , Bilal Muhammad , Shah Junaid Ali , Kaushik Ajeet , Teissedre Pierre-Louis , Kujawska Małgorzata
Published: June 2022

Parkinson’s disease (PD) and other chronic and debilitating neurodegenerative diseases (NDs) impose a substantial medical, emotional, and financial burden on individuals and society. The origin of PD is unknown due to a complex combination of hereditary and environmental risk factors. However, over the last several decades, a significant amount of available data from clinical and experimental studies has implicated neuroinflammation, oxidative stress, dysregulated protein degradation, and mitochondrial dysfunction as the primary causes of PD neurodegeneration. The new gene-editing techniques hold great promise for research and therapy of NDs, such as PD, for which there are currently no effective disease-modifying treatments. As a result, gene therapy may offer new treatment options, transforming our ability to treat this disease. We present a detailed overview of novel gene-editing delivery vehicles, which is essential for their successful implementation in both cutting-edge research and prospective therapeutics. Moreover, we review the most recent advancements in CRISPR-based applications and gene therapies for a better understanding of treating PD. We explore the benefits and drawbacks of using them for a range of gene-editing applications in the brain, emphasizing some fascinating possibilities.
Desire, Delirium, and Revolutionary Love: Deleuzian Feminist Possibilities
Authors: Sholtz Janae
Published: June 2022

In Deleuze and Guattari’s Anti-Oedipus volumes, revolution, social transformation, and the possibility of a new future are all linked to desire: minimally, to the freeing of desire from the false refuges of Oedipalization and its constructs of molar sexuality. Everywhere, they seek to uncover the potential of desire, sexuality, and love, asking us to consider that what we take to be the most personal is impersonal, how the most intimate is the collective and social. Thus, it calls us to rethink our material and affective relations and reconceptualize the sphere of intimacy itself. I develop the concepts of delirium and revolutionary love, suggesting that we interpret these as perpetual processes of transformation and conjugation, initiating relations of intimacy and advocate for more nuanced, complex forms of subjectivity and to become more sensitive to the varying relational complexes within a given space. Revolutionary love gains its newness from both the extension of Deleuzian desire and from its return to several heritages of feminisms which have themselves been marginalized in the forward sweep of new materialist and posthumanist discussions. The point is to sharpen our focus on the conditions that produce certain social bodies, certain kinds of consciousness, and certain molar identities—not to deny the realities of the socius or reject subjectivity, but to move from a majoritarian to a minoritarian politics that widens our purview of what forces and desires exist within these spaces so that we may transform and build less fascistic, more attuned relational complexes.
Muay Thai, Psychological Well-Being, and Cultivation of Combat-Relevant Affordances
Authors: Croom Adam M.
Published: June 2022

Some philosophers argue that martial arts training is maladaptive, contributes to psychological illness, and provides a social harm, whereas others argue that martial arts training is adaptive, contributes to psychological wellness, and provides a social benefit. This debate is important to scholars and the general public since beliefs about martial arts training can have a real impact on how we evaluate martial artists for job opportunities and career advancement, and in general, how we treat martial artists from different cultures in our communities. This debate is also important for children and adults that have considered enrolling in martial arts training programs but remain uncertain about potential outcomes of training due to the lack of research in this area. This article therefore contributes to the literature on martial arts by (1) outlining a framework that characterizes psychological well-being in terms of five elements, (2) discussing how results from empirical research support the hypothesis that Muay Thai training can contribute to psychological well-being by contributing to all five component elements, (3) discussing the psychological benefits of martial arts training from the perspective of an Everlast Master Instructor, and (4) discussing how martial arts training involves the cultivation of combat-relevant affordances.
Fluorescence and Phosphorescence of Flavylium Cation Analogues of Anthocyanins
Authors: Silva Gustavo T. M. , Silva Cassio P. , Silva Karen M. , Pioli Renan M. , Costa Tássia S. , Marto Vinícius V. , Freitas Adilson A. , Rozendo Jennifer , Martins Lucas M. O. S. , Cavalcante Victor F. , Sun Liuqing , Aquino Adelia J. A. , Carneiro Vânia M. T. , Quina Frank H.
Published: June 2022

Fluorescence spectra and lifetimes were determined for 16 synthetic flavylium cation analogues of anthocyanin plant pigments in dry acetonitrile acidified with trifluoroacetic acid (TFA). Phosphorescence was also observed from the lowest excited triplet state for all of the flavylium cations at 77 K in a rigid TFA-acidified isopropanol glass. The fluorescence quantum yields and lifetimes depend in a systematic manner on the nature and position of the substituents on the flavylium chromophore and three specific substitution patterns associated with significant decreases in the fluorescence quantum yield were identified. A 4′-bromo or 4′-iodo substituent in the B-ring of the flavylium cation produced a small but normal heavy-atom effect, reducing the fluorescence quantum yield and the phosphorescence lifetime relative to analogues without the halogen atom. In contrast, three flavylium cations with a 3′-bromo substituent exhibited an “inverse” heavy atom effect, i.e., an increase in the fluorescence quantum yield rather than a decrease, which was rationalized on the basis of the nodal properties of the natural transition orbitals (NTOs) involved in the S0→S1 radiative transition.