bluuebunny/crossref_metadata_2025 huggingface dataset:
Ag Catalysts Supported on CeO2, MnO2 and CeMnOx Mixed Oxides for Selective Catalytic Reduction of NO by C3H6
Authors: La Greca Eleonora , Kharlamova Tamara S. , Grabchenko Maria V. , Consentino Luca , Savenko Daria Yu , Pantaleo Giuseppe , Kibis Lidiya S. , Stonkus Olga A. , Vodyankina Olga V. , Liotta Leonarda Francesca
Published: February 2023

In the present study CeO2, MnO2 and CeMnOx mixed oxide (with molar ratio Ce/Mn = 1) were prepared by sol-gel method using citric acid as a chelating agent and calcined at 500 °C. The silver catalysts (1 wt.% Ag) over the obtained supports were synthesized by the incipient wetness impregnation method with [Ag(NH3)2]NO3 aqueous solution. The selective catalytic reduction of NO by C3H6 was investigated in a fixed-bed quartz reactor using a reaction mixture composed of 1000 ppm NO, 3600 ppm C3H6, 10 vol.% O2, 2.9 vol.% H2 and He as a balance gas, at WHSV of 25,000 mL g−1 h−1.The physical-chemical properties of the as-prepared catalysts were studied by several characterization techniques, such as X-ray fluorescence analysis, nitrogen adsorption/desorption, X-ray analysis, Raman spectroscopy, transmission electron microscopy with analysis of the surface composition by X-ray energy dispersive spectroscopy and X-ray photo-electron spectroscopy. Silver oxidation state and its distribution on the catalysts surface as well as the support microstructure are the main factors determining the low temperature activity in NO selective catalytic reduction. The most active Ag/CeMnOx catalyst (NO conversion at 300 °C is 44% and N2 selectivity is ~90%) is characterized by the presence of the fluorite-type phase with high dispersion and distortion. The characteristic “patchwork” domain microstructure of the mixed oxide along with the presence of dispersed Ag+/Agnδ+ species improve the low-temperature catalyst of NO reduction by C3H6 performance compared to Ag/CeO2 and Ag/MnOx systems.
Construction of CNT-MgO-Ag-BaO Nanocomposite with Enhanced Field Emission and Hydrogen Sensing Performances
Authors: Liu Xingzhen , Qian Weijin , Chen Yawei , Dong Mingliang , Yu Taxue , Huang Weijun , Dong Changkun
Published: February 2023

CNTs and CNT-MgO, CNT-MgO-Ag, and CNT-MgO-Ag-BaO nanocomposites were grown on alloy substrates using an electrophoretic deposition method and their field emission (FE) and hydrogen sensing performances were investigated. The obtained samples were characterized by SEM, TEM, XRD, Raman, and XPS characterizations. The CNT-MgO-Ag-BaO nanocomposites showed the best FE performance with turn-on and threshold fields of 3.32 and 5.92 V.μm−1, respectively. The enhanced FE performances are mainly attributed to the reductions of the work function, and the enhancement of the thermal conductivity and emission sites. The current fluctuation of CNT-MgO-Ag-BaO nanocomposites was only 2.4% after a 12 h test at the pressure of 6.0 × 10−6 Pa. In addition, for the hydrogen sensing performances, the CNT-MgO-Ag-BaO sample showed the best increase in amplitude of the emission current among all the samples, with the mean IN increases of 67%, 120%, and 164% for 1, 3, and 5 min emissions, respectively, under the initial emission currents of about 1.0 μA.
Correction: Moumin et al. Usual Nutrient Intake Distribution and Prevalence of Inadequacy among Australian Children 0–24 Months: Findings from the Australian Feeding Infants and Toddlers Study (OzFITS) 2021. Nutrients 2022, 14, 1381
Authors: Moumin Najma A. , Netting Merryn J. , Golley Rebecca K. , Mauch Chelsea E. , Makrides Maria , Green Tim J.
Published: February 2023

The authors would like to correct an error in their recently published paper [...]
Low Dietary Variety Is Associated with Incident Frailty in Older Adults during the Coronavirus Disease 2019 Pandemic: A Prospective Cohort Study in Japan
Authors: Yokoro Miyuki , Otaki Naoto , Yano Megumu , Imamura Tomomi , Tanino Norikazu , Fukuo Keisuke
Published: February 2023

Background: Stagnation of social activity due to the COVID-19 pandemic probably reduces motivation to maintain a healthy diet. It is important to report on the dietary changes observed in older adults during a period of restriction on outings and to clarify the relationship between dietary variety and frailty. This one-year follow-up study examined the association between frailty and dietary variety during the COVID-19 pandemic. Methods: Baseline and follow-up surveys were conducted in August 2020 and August 2021, respectively. The follow-up survey was distributed by mail to 1635 community-dwelling older adults aged ≥65 years. Of the 1235 respondents, 1008 respondents who were non-frail at baseline are included in this study. Dietary variety was examined using a dietary variety score developed for older adults. Frailty was assessed using a five-item frailty screening tool. The outcome was frailty incidence. Results: In our sample, 108 subjects developed frailty. A linear regression analysis revealed a significant association between dietary variety score and frailty score (β, −0.032; 95% CI, −0.064 to −0.001; p = 0.046). This association was also significant in Model 1, adjusted for sex and age, (β, −0.051; 95% CI, −0.083 to −0.019; p = 0.002) and in a multivariate analysis that added adjustments for living alone, smoking, alcohol use, BMI, and existing conditions to Model 1 (β, −0.045; 95% CI, −0.078 to −0.012; p = 0.015). Conclusions: A low dietary variety score was associated with an increased frailty score during the COVID-19 pandemic. The restricted daily routine caused by the COVID-19 pandemic will probably continue to have a long-term effect in terms of reduced dietary variety. Thus, vulnerable populations, such as older adults, might require dietary support.
Bifidobacterium bifidum CCFM1163 Alleviated Cathartic Colon by Regulating the Intestinal Barrier and Restoring Enteric Nerves
Authors: Tang Nan , Yu Qiangqing , Mei Chunxia , Wang Jialiang , Wang Linlin , Wang Gang , Zhao Jianxin , Chen Wei
Published: February 2023

Cathartic colon (CC), a type of slow-transit constipation caused by the long-term use of stimulant laxatives, does not have a precise and effective treatment. This study aimed to evaluate the ability of Bifidobacterium bifidum CCFM1163 to relieve CC and to investigate its underlying mechanism. Male C57BL/6J mice were treated with senna extract for 8 weeks, followed by a 2-week treatment with B. bifidum CCFM1163. The results revealed that B. bifidum CCFM1163 effectively alleviated CC symptoms. The possible mechanism of B. bifidum CCFM1163 in relieving CC was analyzed by measuring the intestinal barrier and enteric nervous system (ENS)-related indices and establishing a correlation between each index and gut microbiota. The results indicated that B. bifidum CCFM1163 changed the gut microbiota by significantly increasing the relative abundance of Bifidobacterium, Faecalibaculum, Romboutsia, and Turicibacter as well as the content of short-chain fatty acids, especially propionic acid, in the feces. This increased the expression of tight junction proteins and aquaporin 8, decreased intestinal transit time, increased fecal water content, and relieved CC. In addition, B. bifidum CCFM1163 also increased the relative abundance of Faecalibaculum in feces and the expression of enteric nerve marker proteins to repair the ENS, promote intestinal motility, and relieve constipation.
Low FODMAP Diet Relieves Visceral Hypersensitivity and Is Associated with Changes in Colonic Microcirculation in Water Avoidance Mice Model
Authors: Hu Chenmin , Yan Chenxi , Wu Yuhao , Tao Enfu , Guo Rui , Zhu Zhenya , Chen Xiaolong , Fang Marong , Jiang Mizu
Published: February 2023

(1) Background: Irritable bowel syndrome (IBS) is a global public health problem, the pathogenesis of which has not been fully explored. Limiting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can relieve symptoms in some patients with IBS. Studies have shown that normal microcirculation perfusion is necessary to maintain the primary function of the gastrointestinal system. Here, we hypothesized that IBS pathogenesis might be related to abnormalities in colonic microcirculation. A low-FODMAP diet could alleviate visceral hypersensitivity (VH) by improving colonic microcirculation; (2) Methods: C57BL/6 mice were raised to establish an IBS-like rodent model using water avoidance (WA) stress or SHAM-WA as a control, one hour per day for ten days. The mice in the WA group were administered different levels of the FODMAP diet: 2.1% regular FODMAP (WA-RF), 10% high FODMAP diet (WA-HF), 5% medium FODMAP diet (WA-MF), and 0% low FODMAP diet (WA-LF) for the following 14 days. The body weight and food consumption of the mice were recorded. Visceral sensitivity was measured as colorectal distention (CRD) using the abdominal withdrawal reflex (AWR) score. Colonic microcirculation was assessed using laser speckle contrast imaging (LCSI). Vascular endothelial-derived growth factor (VEGF) was detected using immunofluorescence staining; (3) Results: The threshold values of CRD pressure in the WA-RF, WA-HF, and WA-MF groups were significantly lower than those in the SHAM-WA group. Moreover, we observed that colonic microcirculation perfusion decreased, and the expression of VEGF protein increased in these three groups of mice. Interestingly, a low-FODMAP dietary intervention could reverse this situation. Specifically, a low-FODMAP diet increased colonic microcirculation perfusion, reduced VEGF protein expression in mice, and increased the threshold of VH. There was a significant positive correlation between colonic microcirculation and threshold for VH; (4) Conclusions: These results demonstrate that a low-FODMAP diet can alter VH by affecting colonic microcirculation. Changes in intestinal microcirculation may be related to VEGF expression.
Nuts, Energy Balance and Body Weight
Authors: Baer David J. , Dalton Michelle , Blundell John , Finlayson Graham , Hu Frank B.
Published: February 2023

Over several decades, the health benefits of consuming nuts have been investigated, resulting in a large body of evidence that nuts can reduce the risk of chronic diseases. The consumption of nuts, being a higher-fat plant food, is restricted by some in order to minimize weight gain. In this review, we discuss several factors related to energy intake from nuts, including food matrix and its impact on digestibility, and the role of nuts in regulating appetite. We review the data from randomized controlled trials and observational studies conducted to examine the relationship between nut intake and body weight or body mass index. Consistently, the evidence from RCTs and observational cohorts indicates that higher nut consumption does not cause greater weight gain; rather, nuts may be beneficial for weight control and prevention of long-term weight gain. Multiple mechanisms likely contribute to these findings, including aspects of nut composition which affect nutrient and energy availability as well as satiety signaling.
Fecal Calprotectin Elevations Associated with Food Intolerance/Malabsorption Are Significantly Reduced with Targeted Diets
Authors: Schnedl Wolfgang J. , Michaelis Simon , Enko Dietmar , Mangge Harald
Published: February 2023

Inflammatory bowel disease (IBD) involves two clinically defined entities, namely Crohn’s disease and ulcerative colitis. Fecal calprotectin (FCAL) is used as a marker to distinguish between organic IBD and functional bowel disease in disorders of the irritable bowel syndrome (IBS) spectrum. Food components may affect digestion and cause functional abdominal disorders of the IBS spectrum. In this retrospective study, we report on FCAL testing to search for IBD in 228 patients with disorders of the IBS spectrum caused by food intolerances/malabsorption. Included were patients with fructose malabsorption (FM), histamine intolerance (HIT), lactose intolerance (LIT), and H. pylori infection. We found elevated FCAL values in 39 (17.1%) of 228 IBS patients with food intolerance/malabsorption and H. pylori infection. Within these, fourteen patients were lactose intolerant, three showed fructose malabsorption, and six had histamine intolerance. The others had combinations of the above conditions: five patients had LIT and HIT, two patients had LIT and FM, and four had LIT and H. pylori. In addition, there were individual patients with other double or triple combinations. In addition to LIT, IBD was suspected in two patients due to continuously elevated FCAL, and then found via histologic evaluation of biopsies taken during colonoscopy. One patient with elevated FCAL had sprue-like enteropathy caused by the angiotensin receptor-1 antagonist candesartan. When screening for study subjects concluded, 16 (41%) of 39 patients with initially elevated FCAL agreed to voluntarily control FCAL measurements, although symptom-free and -reduced, following the diagnosis of intolerance/malabsorption and/or H. pylori infection. After the initiation of a diet individualized to the symptomatology and eradication therapy (when H. pylori was detected), FCAL values were significantly lowered or reduced to be within the normal range.
Infant and Young Child Feeding Practices and Health
Authors: Berti Cristiana , Socha Piotr
Published: February 2023

Early childhood feeding practices are fundamental for a child’s healthy growth, development and potential [...]
School Gardening and Health and Well-Being of School-Aged Children: A Realist Synthesis
Authors: Holloway Timothy P. , Dalton Lisa , Hughes Roger , Jayasinghe Sisitha , Patterson Kira A. E. , Murray Sandra , Soward Robert , Byrne Nuala M. , Hills Andrew P. , Ahuja Kiran D. K.
Published: February 2023

School environments can create healthy settings to foster children’s health and well-being. School gardening is gaining popularity as an intervention for healthier eating and increased physical activity. We used a systematic realist approach to investigate how school gardens improve health and well-being outcomes for school-aged children, why, and in what circumstances. The context and mechanisms of the specific school gardening interventions (n = 24) leading to positive health and well-being outcomes for school-aged children were assessed. The impetus of many interventions was to increase fruit and vegetable intake and address the prevention of childhood obesity. Most interventions were conducted at primary schools with participating children in Grades 2 through 6. Types of positive outcomes included increased fruit and vegetable consumption, dietary fiber and vitamins A and C, improved body mass index, and improved well-being of children. Key mechanisms included embedding nutrition-based and garden-based education in the curriculum; experiential learning opportunities; family engagement and participation; authority figure engagement; cultural context; use of multi-prong approaches; and reinforcement of activities during implementation. This review shows that a combination of mechanisms works mutually through school gardening programs leading to improved health and well-being outcomes for school-aged children.
Laser Beam Jitter Control Based on a LabVIEW FPGA Control System
Authors: Zhang Delin , Cheng Jingxin , Xia Yuanqin
Published: February 2023

The thermal blooming effect, platform jitter, and other effects of laser beam propagation cause serious deviation, which will have a negative impact on laser tracking systems. It is important to ensure that the laser beam does not deviate. Based on a fast steering mirror, a CMOS camera, and a Flex RIO system, a laser beam jitter control system is designed and implemented. The error is detected by camera and compensated for by the fast steering mirror (FSM), which is controlled by the Flex RIO device. By using LabVIEW and MATLAB, a closed loop model is realized. The results show that the system response is highly stabilized and has a short rise time, providing a reference for engineering applications.
Designing a Next-Generation Multiepitope-Based Vaccine against Staphylococcus aureus Using Reverse Vaccinology Approaches
Authors: Mahapatra Soumya Ranjan , Dey Jyotirmayee , Raj T. Kiran , Misra Namrata , Suar Mrutyunjay
Published: February 2023

Staphylococcus aureus is a human bacterial pathogen that can cause a wide range of symptoms. As virulent and multi-drug-resistant strains of S. aureus have evolved, invasive S. aureus infections in hospitals and the community have become one of the leading causes of mortality and morbidity. The development of novel techniques is therefore necessary to overcome this bacterial infection. Vaccines are an appropriate alternative in this context to control infections. In this study, the collagen-binding protein (CnBP) from S. aureus was chosen as the target antigen, and a series of computational methods were used to find epitopes that may be used in vaccine development in a systematic way. The epitopes were passed through a filtering pipeline that included antigenicity, toxicity, allergenicity, and cytokine inducibility testing, with the objective of identifying epitopes capable of eliciting both T and B cell-mediated immune responses. To improve vaccine immunogenicity, the final epitopes and phenol-soluble modulin α4 adjuvant were fused together using appropriate linkers; as a consequence, a multiepitope vaccine was developed. The chosen T cell epitope ensemble is expected to cover 99.14% of the global human population. Furthermore, docking and dynamics simulations were used to examine the vaccine’s interaction with the Toll-like receptor 2 (TLR2), revealing great affinity, consistency, and stability between the two. Overall, the data indicate that the vaccine candidate may be extremely successful, and it will need to be evaluated in experimental systems to confirm its efficiency.
The Devastating Rice Blast Airborne Pathogen Magnaporthe oryzae—A Review on Genes Studied with Mutant Analysis
Authors: Tan Jinyi , Zhao Haikun , Li Josh , Gong Yihan , Li Xin
Published: February 2023

Magnaporthe oryzae is one of the most devastating pathogenic fungi that affects a wide range of cereal plants, especially rice. Rice blast disease causes substantial economic losses around the globe. The M. oryzae genome was first sequenced at the beginning of this century and was recently updated with improved annotation and completeness. In this review, key molecular findings on the fungal development and pathogenicity mechanisms of M. oryzae are summarized, focusing on fully characterized genes based on mutant analysis. These include genes involved in the various biological processes of this pathogen, such as vegetative growth, conidia development, appressoria formation and penetration, and pathogenicity. In addition, our syntheses also highlight gaps in our current understanding of M. oryzae development and virulence. We hope this review will serve to improve a comprehensive understanding of M. oryzae and assist disease control strategy designs in the future.
Design, Synthesis, and Neuroprotective Activity of Phenoxyindole Derivatives on Antiamyloid Beta (Aβ) Aggregation, Antiacetylcholinesterase, and Antioxidant Activities
Authors: Laivut Somjate , Moongkarndi Primchanien , Kitphati Worawan , Rukthong Pattarawit , Sathirakul Korbtham , Sripha Kittisak
Published: February 2023

In this investigation, a number of phenoxyindole derivatives were designed, synthesized, and tested for their neuroprotective ability on SK-N-SH cells against Aβ42-induced cell death and biologically specific activities involved in anti-Aβ aggregation, anti-AChE, and antioxidant effects. The proposed compounds, except compounds 9 and 10, could protect SK-N-SH cells at the IC50 of anti-Aβ aggregation with cell viability values ranging from 63.05% ± 2.70% to 87.90% ± 3.26%. Compounds 3, 5, and 8 demonstrated striking relationships between the %viability of SK-N-SH cells and IC50 values of anti-Aβ aggregation and antioxidants. No significant potency of all synthesized compounds against AChE was found. Among them, compound 5 showed the strongest anti-Aβ and antioxidant properties with IC50 values of 3.18 ± 0.87 and 28.18 ± 1.40 μM, respectively. The docking data on the monomeric Aβ peptide of compound 5 demonstrated good binding at regions involved in the aggregation process, and the structural feature made it possible to be a superior radical scavenger. The most effective neuroprotectant belonged to compound 8, with a cell viability value of 87.90% ± 3.26%. Its unique mechanisms for enhancing the protective impact may serve additional purposes since it demonstrated mild biological-specific effects. In silico prediction of CNS penetration shows strong passive penetration ability across the blood–brain barrier from blood vessels to the CNS for compound 8. In light of our findings, compounds 5 and 8 appeared as potentially intriguing lead compounds for new therapeutic approaches to Alzheimer’s disease. More in vivo testing will be revealed in due course.
Probiotic-Fermented Camel Milk Attenuates Neurodegenerative Symptoms via SOX5/miR-218 Axis Orchestration in Mouse Models
Authors: Khalifa Ashraf , Ibrahim Hairul Islam Mohamed , Sheikh Abdullah , Khalil Hany Ezzat
Published: February 2023

Multiple sclerosis is an autoimmune-mediated myelin damage disorder in the central nervous system that is widespread among neurological patients. It has been demonstrated that several genetic and epigenetic factors control autoimmune encephalomyelitis (EAE), a murine model of MS, through CD4+ T-cell population quantity. Alterations in the gut microbiota influence neuroprotectiveness via unexplored mechanisms. In this study, the ameliorative effect of Bacillus amyloliquefaciens fermented in camel milk (BEY) on an autoimmune-mediated neurodegenerative model using myelin oligodendrocyte glycoprotein/complete fraud adjuvant/pertussis toxin (MCP)-immunized C57BL6j mice is investigated. Anti-inflammatory activity was confirmed in the in vitro cell model, and inflammatory cytokines interleukins IL17 (from EAE 311 to BEY 227 pg/mL), IL6 (from EAE 103 to BEY 65 pg/mL), IFNγ (from EAE 423 to BEY 243 pg/mL) and TGFβ (from EAE 74 to BEY 133 pg/mL) were significantly reduced in BEY-treated mice. The epigenetic factor miR-218-5P was identified and confirmed its mRNA target SOX-5 using in silico tools and expression techniques, suggesting SOX5/miR-218-5p could serve as an exclusive diagnostic marker for MS. Furthermore, BEY improved the short-chain fatty acids, in particular butyrate (from 0.57 to 0.85 µM) and caproic (from 0.64 to 1.33 µM) acids, in the MCP mouse group. BEY treatment significantly regulated the expression of inflammatory transcripts in EAE mice and upregulated neuroprotective markers such as neurexin (from 0.65- to 1.22-fold) (p < 0.05), vascular endothelial adhesion molecules (from 0.41- to 0.76-fold) and myelin-binding protein (from 0.46- to 0.89-fold) (p < 0.03). These findings suggest that BEY could be a promising clinical approach for the curative treatment of neurodegenerative diseases and could promote the use of probiotic food as medicine.
Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats
Authors: Bernat Brigitta , Erdelyi Rita , Fazekas Laszlo , Garami Greta , Szekeres Reka Maria , Takacs Barbara , Bombicz Mariann , Varga Balazs , Sarkany Fruzsina , Raduly Arnold Peter , Romanescu Dana Diana , Papp Zoltan , Toth Attila , Szilvassy Zoltan , Juhasz Bela , Priksz Daniel
Published: February 2023

Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40–160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias.
Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice
Authors: Wang Qian , Peng Dewei , Huang Bingyu , Men Lintong , Jiang Tao , Huo Shengqi , Wang Moran , Guo Junyi , Lv Jiagao , Lin Li
Published: February 2023

Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of potassium oxonate and adenine every other day for six weeks. Notopterol (20 mg/kg) and allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that hyperuricemia dampened heart function and reduced exercise capacity. Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in uric acid-treated H9c2 cells. Notopterol administration significantly suppressed expression levels of pyroptosis associated proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in uric acid-induced NLRP3 inflammatory signals. Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under uric acid stimulation. Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice.
Dual-Labelled Nanoparticles Inform on the Stability of Fluorescent Labels In Vivo
Authors: Roussel Sabrina , Grenier Philippe , Chénard Valérie , Bertrand Nicolas
Published: February 2023

Fluorescent labelling is commonly used to monitor the biodistribution of nanomedicines. However, meaningful interpretation of the results requires that the fluorescent label remains attached to the nanomedicine. In this work, we explore the stability of three fluorophores (BODIPY650, Cyanine 5 and AZ647) attached to polymeric hydrophobic biodegradable anchors. Using dual-labelled poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) nanoparticles that are both radioactive and fluorescent, we investigated how the properties of the fluorophores impact the stability of the labelling in vitro and in vivo. Results suggest that the more hydrophilic dye (AZ647) is released faster from nanoparticles, and that this instability results in misinterpretation of in vivo data. While hydrophobic dyes are likely more suitable to track nanoparticles in biological environments, quenching of the fluorescence inside the nanoparticles can also introduce artefacts. Altogether, this work raises awareness about the importance of stable labelling methods when investigating the biological fate of nanomedicines.
Current Treatments and New, Tentative Therapies for Parkinson’s Disease
Authors: Pardo-Moreno Teresa , García-Morales Victoria , Suleiman-Martos Sami , Rivas-Domínguez Antonio , Mohamed-Mohamed Himan , Ramos-Rodríguez Juan José , Melguizo-Rodríguez Lucía , González-Acedo Anabel
Published: February 2023

Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson’s disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients.
Recent Progress of Lipid Nanoparticles-Based Lipophilic Drug Delivery: Focus on Surface Modifications
Authors: Seo Yoseph , Lim Hayeon , Park Hyunjun , Yu Jiyun , An Jeongyun , Yoo Hah Young , Lee Taek
Published: February 2023

Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic and are used for treating diseases through various delivery routes, including skin absorption, oral administration, and injection. However, as lipophilic drugs have a low solubility in the human body, drug delivery systems (DDSs) are being actively developed to increase drug bioavailability. Liposomes, micro-sponges, and polymer-based nanoparticles have been proposed as DDS carriers for lipophilic drugs. However, their instability, cytotoxicity, and lack of targeting ability limit their commercialization. Lipid nanoparticles (LNPs) have fewer side effects, excellent biocompatibility, and high physical stability. LNPs are considered efficient vehicles of lipophilic drugs owing to their lipid-based internal structure. In addition, recent LNP studies suggest that the bioavailability of LNP can be increased through surface modifications, such as PEGylation, chitosan, and surfactant protein coating. Thus, their combinations have an abundant utilization potential in the fields of DDSs for carrying lipophilic drugs. In this review, the functions and efficiencies of various types of LNPs and surface modifications developed to optimize lipophilic drug delivery are discussed.
Smart Polymeric Nanoparticles in Cancer Immunotherapy
Authors: Yu Zhecheng , Shen Xingyue , Yu Han , Tu Haohong , Chittasupho Chuda , Zhao Yunqi
Published: February 2023

Cancer develops with unexpected mutations and causes death in many patients. Among the different cancer treatment strategies, immunotherapy is promising with the benefits of high specificity and accuracy, as well as modulating immune responses. Nanomaterials can be used to formulate drug delivery carriers for targeted cancer therapy. Polymeric nanoparticles used in the clinic are biocompatible and have excellent stability. They have the potential to improve therapeutic effects while significantly reducing off-target toxicity. This review classifies smart drug delivery systems based on their components. Synthetic smart polymers used in the pharmaceutical industry, including enzyme-responsive, pH-responsive, and redox-responsive polymers, are discussed. Natural polymers derived from plants, animals, microbes, and marine organisms can also be used to construct stimuli-responsive delivery systems with excellent biocompatibility, low toxicity, and biodegradability. The applications of smart or stimuli-responsive polymers in cancer immunotherapies are discussed in this systemic review. We summarize different delivery strategies and mechanisms that can be used in cancer immunotherapy and give examples of each case.
Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy
Authors: Wilton-Clark Harry , Yokota Toshifumi
Published: February 2023

Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/5000 boys globally, characterized by progressive muscle breakdown and eventual death, with an average lifespan in the mid–late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.
Synthesis of Schiff Bases Containing Phenol Rings and Investigation of Their Antioxidant Capacity, Anticholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibition Properties
Authors: Aytac Sertan , Gundogdu Ozlem , Bingol Zeynebe , Gulcin İlhami
Published: February 2023

The widespread usage of Schiff bases in chemistry, industry, medicine, and pharmacy has increased interest in these compounds. Schiff bases and derivative compounds have important bioactive properties. Heterocyclic compounds containing phenol derivative groups in their structure have the potential to capture free radicals that can cause diseases. In this study, we designed and synthesized eight Schiff bases (10–15) and hydrazineylidene derivatives (16–17), which contain phenol moieties and have the potential to be used as synthetic antioxidants, for the first time using microwave energy. Additionally, the antioxidant effects of Schiff bases (10–15) and hydrazineylidene derivatives (16–17) were studied using by the bioanalytical methods of 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical (ABTS•+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) scavenging activities, and Fe3+, Cu2+, and Fe3+-TPTZ complex reducing capacities. In the context of studies on antioxidants, Schiff bases (10–15) and hydrazineylidene derivatives (16–17) were found to be as powerful DPPH (IC50: 12.15–99.01 μg/mL) and ABTS•+ (IC50: 4.30–34.65 μg/mL). Additionally, the inhibition abilities of Schiff bases (10–15) and hydrazineylidene derivatives (16–17) were determined towards some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCAs I and II), enzymes that are linked to some global disorders including Alzheimer’s disease (AD), epilepsy, and glaucoma. In the context of studies on enzyme inhibition, it was observed that the synthesized Schiff bases (10–15) and hydrazineylidene derivatives (16–17) inhibited AChE, BChE, hCAs I, and hCA II enzymes with IC50 values in ranges of 16.11–57.75 nM, 19.80–53.31 nM, 26.08 ± 8.53 nM, and 85.79 ± 24.80 nM, respectively. In addition, in light of the results obtained, we hope that this study will be useful and guiding for the evaluation of biological activities in the fields of the food, medical, and pharmaceutical industries in the future.
Virus-like Particle Vaccine Expressing the Respiratory Syncytial Virus Pre-Fusion and G Proteins Confers Protection against RSV Challenge Infection
Authors: Lee Su-Hwa , Chu Ki-Back , Kim Min-Ju , Mao Jie , Eom Gi-Deok , Yoon Keon-Woong , Ahmed Md Atique , Quan Fu-Shi
Published: February 2023

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in children and the elderly. However, there are no effective antiviral drugs or licensed vaccines available for RSV infection. Here, RSV virus-like particle (VLP) vaccines expressing Pre-F, G, or Pre-F and G proteins on the surface of influenza virus matrix protein 1 (M1) were produced using the baculovirus expression system, and their protective efficacy was evaluated in mice. The morphology and successful assembly of VLPs were confirmed by transmission electron microscope (TEM) and Western blot. High levels of serum IgG antibody response were detected in VLP-immunized mice, and significantly higher levels of IgG2a and IgG2b were found in the Pre-F+G VLP immunization group compared to the unimmunized control. Serum-neutralizing activity was higher in the VLP immunization groups compared to the naïve group, with Pre-F+G VLPs demonstrating superior neutralizing activity to the single antigen-expressing VLP groups. Pulmonary IgA and IgG responses were generally comparable across the immunization groups, with VLPs expressing the Pre-F antigen eliciting higher IFN-γ in spleens. The frequencies of eosinophils and IL-4-producing CD4+ T cell populations were substantially lower in the lungs of VLP-immunized mice, with the PreF+G vaccine inducing a significant increase in CD4+ and CD8+ T cells. VLP immunization significantly decreased the viral titer and inflammation in the lungs of mice, with Pre-F+G VLPs conferring the best protection. In conclusion, our present study suggests that the Pre-F+G VLPs could be a potential vaccine candidate against RSV infection.
Novel Approach for the Approximation of Vitamin D3 Pharmacokinetics from In Vivo Absorption Studies
Authors: Żurek Grzegorz , Przybyło Magdalena , Witkiewicz Wojciech , Langner Marek
Published: February 2023

The changing environment and modified lifestyles have meant that many vitamins and minerals are deficient in a significant portion of the human population. Therefore, supplementation is a viable nutritional approach, which helps to maintain health and well-being. The supplementation efficiency of a highly hydrophobic compound such as cholecalciferol (logP > 7) depends predominantly on the formulation. To overcome difficulties associated with the evaluation of pharmacokinetics of cholecalciferol, a method based on the short time absorption data in the clinical study and physiologically based mathematical modeling is proposed. The method was used to compare pharmacokinetics of liposomal and oily formulations of vitamin D3. The liposomal formulation was more effective in elevating calcidiol concentration in serum. The determined AUC value for liposomal vitamin D3 formulation was four times bigger than that for the oily formulation.
Examining General Vaccine Acceptance and COVID-19 Vaccine Intention: Comparison across Pharmacies in California and Ohio
Authors: Mercadante Amanda R. , Chen Aleda M. H. , Chu Vivian , Wong Jason C. , Law Anandi V.
Published: February 2023

Given the complexities surrounding vaccine acceptance of COVID-19 and other vaccines, it is important to determine the underlying health beliefs of patients in order to bridge gaps and promote vaccine confidence. With pharmacies as key hubs for vaccinations and vaccine conversations, examining patient perspectives through the lens of community pharmacy may provide a targeted insight into their patient populations. The primary objectives of this study were to measure COVID-19 vaccine intention and compare vaccine acceptance at pharmacies and clinics between California and Ohio. The secondary objectives included subgroup comparisons of vaccine intention and vaccine acceptance based on demographic characteristics. A previously validated survey instrument (5C survey tool) was administered at pharmacy sites in California and Ohio to examine respondents’ vaccine acceptance (confidence, complacency, constrains, calculation, and collective responsibility). Additional items were added to capture flu and COVID-19 vaccine intention. Reliability and confirmatory factor analysis were completed for the 13-item 5C. Comparisons were made between sites and within different demographic groups. Good reliability (Cronbach’s alpha = 0.768) was found, with nearly all items loading on their hypothesized domains. Respondents from Ohio had significantly higher complacency and constraints domain scores. Highest acceptance was revealed in females, individuals with a Master’s degree or higher, and individuals with the intention to receive a flu vaccine. The adapted 5C is a reasonable tool to measure vaccine intention in English-speaking populations in the US. Certain demographic groups may have lower vaccine acceptance; pharmacists could consider implementing a tool, such as the 5C tool, to identify low acceptance. Given that the 5C tool gathers information on different domains of vaccine acceptance, healthcare professionals could utilize these results to improve trust and vaccine confidence in their patient populations; focused conversations concerning any of the respective domains could best address individual concerns and barriers about vaccinations, notably the COVID-19 and flu vaccines.
Neutral Realism: A New Metaphysical Approach to Representation
Authors: Dyke Heather
Published: February 2023

Metaphysics seeks an account of fundamental reality as it is independent of any observer or point of view. As such, one problem it faces is that any such account is necessarily created by some observer from some point of view. Does this mean that metaphysics is thereby inherently impossible? Or inherently incomplete? I argue that it is possible and it can aim at completeness, but it must acknowledge the contributions made by the human perspective on reality, human cognition, and features of the conceptual and linguistic representations in which it is couched. The idea that we can discover metaphysical insights by investigating concepts and language has had a remarkably tenacious grip on the field of metaphysics. I offer a diagnosis of how this grip took hold and an argument that it should be loosened. I also propose a means of pursuing metaphysical investigation that does not rely on an enquiry into language and that can yield fruitful results.
What Makes the Life of Stressed Plants a Little Easier? Defense Mechanisms against Adverse Conditions
Authors: Muszyńska Ewa , Dziurka Kinga , Labudda Mateusz
Published: February 2023

Plants experience a wide array of external factors, some of which negatively affect their metabolism, growth, and development [...]
Simulation of Photosynthetic Quantum Efficiency and Energy Distribution Analysis Reveals Differential Drought Response Strategies in Two (Drought-Resistant and -Susceptible) Sugarcane Cultivars
Authors: An Dongsheng , Zhao Baoshan , Liu Yang , Xu Zhijun , Kong Ran , Yan Chengming , Su Junbo
Published: February 2023

Selections of drought-tolerant cultivars and drought-stress diagnosis are important for sugarcane production under seasonal drought, which becomes a crucial factor causing sugarcane yield reduction. The main objective of this study was to investigate the differential drought-response strategies of drought-resistant (‘ROC22’) and -susceptible (‘ROC16’) sugarcane cultivars via photosynthetic quantum efficiency (Φ) simulation and analyze photosystem energy distribution. Five experiments were conducted to measure chlorophyll fluorescence parameters under different photothermal and natural drought conditions. The response model of Φ to photosynthetically active radiation (PAR), temperature (T), and the relative water content of the substrate (rSWC) was established for both cultivars. The results showed that the decreasing rate of Φ was higher at lower temperatures than at higher temperatures, with increasing PAR under well-watered conditions. The drought-stress indexes (εD) of both cultivars increased after rSWC decreased to the critical values of 40% and 29% for ‘ROC22’ and ‘ROC16’, respectively, indicating that the photosystem of ‘ROC22’ reacted more quickly than that of ‘ROC16’ to water deficit. An earlier response and higher capability of nonphotochemical quenching (NPQ) accompanied the slower and slighter increments of the yield for other energy losses (ΦNO) for ‘ROC22’ (at day5, with a rSWC of 40%) compared with ‘ROC16’ (at day3, with a rSWC of 56%), indicating that a rapid decrease in water consumption and an increase in energy dissipation involved in delaying the photosystem injury could contribute to drought tolerance for sugarcane. In addition, the rSWC of ‘ROC16’ was lower than that of ‘ROC22’ throughout the drought treatment, suggesting that high water consumption might be adverse to drought tolerance of sugarcane. This model could be applied for drought-tolerance assessment or drought-stress diagnosis for sugarcane cultivars.
Chemopreventive Activity of Ellagitannins from Acer pseudosieboldianum (Pax) Komarov Leaves on Prostate Cancer Cells
Authors: Son Se-Yeon , Choi Jin-Hyeok , Kim Eun-Bin , Yin Jun , Seonu Seo-Yeon , Jin Si-Yeon , Oh Jae-Yoon , Lee Min-Won
Published: February 2023

Several studies have shown that compounds from Acer pseudosieboldianum (Pax) Komarov leaves (APL) display potent anti-oxidative, anti-inflammatory, and anti-proliferative activities. Prostate cancer (PCa) is the most common cancer among older men, and DNA methylation is associated with PCa progression. This study aimed to investigate the chemopreventive activities of the compounds which were isolated from APL on prostate cancer cells and elucidate the mechanisms of these compounds in relation to DNA methylation. One novel ellagitannin [komaniin (14)] and thirteen other known compounds, including glucose derivatives [ethyl-β-D-glucopyranose (3) and (4R)-p-menth-1-ene-7,8-diol 7-O-β-D-glucopyranoside (4)], one phenylpropanoid [junipetrioloside A (5)], three phenolic acid derivatives [ellagic acid-4-β-D-xylopyranoside (1), 4-O-galloyl-quinic acid (2), and gallic acid (8)], two flavonoids [quercetin (11) and kaempferol (12)], and five hydrolysable tannins [geraniin (6), punicafolin (7), granatin B (9), 1,2,3,4,6-penta-galloyl-β-D-glucopyranoside (10), and mallotusinic acid (13)] were isolated from APL. The hydrolyzable tannins (6, 7, 9, 10, 13, and 14) showed potent anti-PCa proliferative and apoptosis-promoting activities. Among the compounds, the ellagitannins in the dehydrohexahydroxydiphenoyl (DHHDP) group (6, 9, 13, and 14), the novel compound 14 showed the most potent inhibitory activity on DNA methyltransferase (DNMT1, 3a and 3b) and glutathione S-transferase P1 methyl removing and re-expression activities. Thus, our results suggested that the ellagitannins (6, 9, 13, and 14) isolated from APL could be a promising treatment option for PCa.