bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Berberine@carbon Dots Nano-Formulation: Synthesis, Characterization and Herbicidal Activity against Echinochloa crus-galli and Amaranthus retroflexus Two Common Species of Weed
Authors: Xu Junhu , Rong Shuang , Qin Ziqi , Shen Guangmao , Wu Yan , Zhang Zan , Qian Kun
Published: December 2022

Berberine (Ber) is easy to synthesize and has a variety of biological and pharmacological activities. At present, the existing studies on berberine have focused predominantly on its antibacterial activity; its herbicidal activity is rarely reported. In addition, there are a number of preparations of berberine, which are not enough to solve its shortcomings of low solubility and biological activity and the difficult storage of berberine. Here, berberine was combined with carbon dots to obtain carbon dots-berberine (CDs-Ber) nano formulation. The fluorescence quenching results showed that the CDs-Ber nano drug delivery system was successfully constructed, and the fluorescence quenching mechanism of the two was static quenching. The bioassay results showed that CDs had no adverse effects on the growth of barnyard grass (Echinochloa crus-galli) and redroot pigweed (Amaranthus retroflexus), and had high biocompatibility. Berberine and CDs-Ber predominantly affected the root growth of barnyard grass and redroot pigweed and could enhance the growth inhibition effect on weeds, to some extent. The results of the protective enzyme system showed that both berberine and CDs-Ber could increase the activities of Superoxide dismutase (SOD), Peroxidase (POD), and Catalase (CAT) in barnyard grass, and CDs-Ber had a stronger stress effect on barnyard grass than berberine. The determination of the number of bacterial communities in the soil after the berberine and CDs-Ber treatments showed that there was no significant difference in the effects of the two, indicating that CDs-Ber would not have more negative impacts on the environment. The CDs-Ber nano formulation improved the biological activity of berberine, enhanced the herbicidal effect, and was relatively safe for soil colonies.
CeO2-Azacrown Conjugate as a Nanoplatform for Combined Radiopharmaceuticals
Authors: Khabirova Sofia , Aleshin Gleb , Plakhova Tatiana , Zubenko Anastasia , Shchukina Anna , Fedorova Olga , Averin Aleksey , Belova Ekaterina , Bazarkina Elena , Kvashnina Kristina , Kalmykov Stepan
Published: December 2022

This study is one of the first attempts to assess CeO2 nanoparticles as a nanoplatform for radiopharmaceuticals with radionuclides. The process of functionalization using a bifunctional azacrown ligand is described, and the resulting conjugates are characterized by IR and Raman spectroscopy. Their complexes with 207Bi show a high stability in medically relevant media, thus encouraging the further study of these conjugates in vivo as potential combined radiopharmaceuticals.
Effect of Different Solvents on Morphology and Gas-Sensitive Properties of Grinding-Assisted Liquid-Phase-Exfoliated MoS2 Nanosheets
Authors: Wang Hao , Xu Xiaojie , Shaymurat Talgar
Published: December 2022

Grinding-assisted liquid-phase exfoliation is a widely used method for the preparation of two-dimensional nanomaterials. In this study, N-methylpyrrolidone and acetonitrile, two common grinding solvents, were used during the liquid-phase exfoliation for the preparation of MoS2 nanosheets. The morphology and structure of MoS2 nanosheets were analyzed via scanning electron microscopy, X-ray diffraction, and Raman spectroscopy. The effects of grinding solvents on the gas-sensing performance of the MoS2 nanosheets were investigated for the first time. The results show that the sensitivities of MoS2 nanosheet exfoliation with N-methylpyrrolidone were 2.4-, 1.4-, 1.9-, and 2.7-fold higher than exfoliation with acetonitrile in the presence of formaldehyde, acetone, and ethanol and 98% relative humidity, respectively. MoS2 nanosheet exfoliation with N-methylpyrrolidone also has fast response and recovery characteristics to 50–1000 ppm of CH2O. Accordingly, although N-methylpyrrolidone cannot be removed completely from the surface of MoS2, it has good gas sensitivity compared with other samples. Therefore, N-methylpyrrolidone is preferred for the preparation of gas-sensitive MoS2 nanosheets in grinding-assisted liquid-phase exfoliation. The results provide an experimental basis for the preparation of two-dimensional materials and their application in gas sensors.
All-Aerosol-Jet-Printed Carbon Nanotube Transistor with Cross-Linked Polymer Dielectrics
Authors: Mishra Bhagyashree , Chen Yihong Maggie
Published: December 2022

The printability of reliable gate dielectrics and their influence on the stability of the device are some of the primary concerns regarding the practical application of printed transistors. Major ongoing research is focusing on the structural properties of dielectric materials and deposition parameters to reduce interface charge traps and hysteresis caused by the dielectric–semiconductor interface and dielectric bulk. This research focuses on improving the dielectric properties of a printed polymer material, cross-linked polyvinyl phenol (crPVP), by optimizing the cross-linking parameters as well as the aerosol jet printability. These improvements were then applied to the fabrication of completely printed carbon nanotube (CNT)-based thin-film transistors (TFT) to reduce the gate threshold voltage (Vth) and hysteresis in Vth during device operation. Finally, a fully aerosol-jet-printed CNT device was demonstrated using a 2:1 weight ratio of PVP with the cross-linker poly(melamine-co-formaldehyde) methylated (PMF) in crPVP as the dielectric material. This device shows significantly less hysteresis and can be operated at a gate threshold voltage as low as −4.8 V with an on/off ratio of more than 104.
BN-PVDF/rGO-PVDF Laminate Nanocomposites for Energy Storage Applications
Authors: Agbabiaka Okikiola Ganiu , Adegun Miracle Hope , Chan Kit-Ying , Zhang Heng , Shen Xi , Kim Jang-Kyo
Published: December 2022

The increasing demand for high energy storage devices calls for concurrently enhanced dielectric constants and reduced dielectric losses of polymer dielectrics. In this work, we rationally design dielectric composites comprising aligned 2D nanofillers of reduced graphene oxide (rGO) and boron nitride nanosheets (BNNS) in a polyvinylidene fluoride (PVDF) matrix through a novel press-and-fold technique. Both nanofillers play different yet complementary roles: while rGO is designed to enhance the dielectric constant through charge accumulation at the interfaces with polymer, BNNS suppress the dielectric loss by preventing the mobility of free electrons. The microlaminate containing eight layers each of rGO/PVDF and BNNS/PVDF films exhibits remarkable dielectric performance with a dielectric constant of 147 and an ultralow dielectric loss of 0.075, due to the synergistic effect arising from the alternatingly electrically conductive and insulating films. Consequently, a maximum energy density of 3.5 J/cm3—about 18 times the bilayer composite counterpart—is realized. The high thermal conductivities of both nanofillers and their alignment endow the microlaminate with an excellent in-plane thermal conductivity of 6.53 Wm−1K−1, potentially useful for multifunctional applications. This work offers a simple but effective approach to fabricating a composite for high dielectric energy storage using two different 2D nanofillers.
Photodynamics of Bright Subnanosecond Emission from Pure Single-Photon Sources in Hexagonal Boron Nitride
Authors: Gritsienko Alexander V. , Duleba Aliaksandr , Pugachev Mikhail V. , Kurochkin Nikita S. , Vlasov Igor I. , Vitukhnovsky Alexei G. , Kuntsevich Alexandr Yu.
Published: December 2022

Bright and stable emitters of single indistinguishable photons are crucial for quantum technologies. The origin of the promising bright emitters recently observed in hexagonal boron nitride (hBN) still remains unclear. This study reports pure single-photon sources in multi-layered hBN at room temperature that demonstrate high emission rates. The quantum emitters are introduced with argon beam treatment and air annealing of mechanically exfoliated hBN flakes with thicknesses of 5–100 nm. Spectral and time-resolved measurements reveal the emitters have more than 1 GHz of excited-to-ground state transition rate. The observed photoswitching between dark and bright states indicates the strong sensitivity of the emitter to the electrostatic environment and the importance of the indirect excitation for the photodynamics.
Polymerization Kinetics of Acrylic Photopolymer Loaded with Graphene-Based Nanomaterials for Additive Manufacturing
Authors: Lopez de Armentia Sara , Abenojar Juana , Ballesteros Yolanda , del Real Juan Carlos , Dunne Nicholas , Paz Eva
Published: December 2022

Graphene-based nanomaterials (GBN) can provide attractive properties to photocurable resins used in 3D printing technologies such as improved mechanical properties, electrical and thermal conductivity, and biological capabilities. However, the presence of GBN can affect the printing process (e.g., polymerization, dimensional stability, or accuracy), as well as compromising the quality of structures. In this study an acrylic photocurable resin was reinforced with GBN, using methyl methacrylate (MMA) to favor homogenous dispersion of the nanomaterials. The objective was to investigate the influence that the incorporation of GBN and MMA has on polymerization kinetics by Differential Scanning Calorimetry using Model Free Kinetics, ultra-violet (UV) and thermal triggered polymerization. It was found that MMA catalyzed polymerization reaction by increasing the chain’s mobility. In the case of GBNs, graphene demonstrated to inhibit both, thermally and UV triggered polymerization, whilst graphene oxide showed a double effect: it chemically inhibited the polymerization reaction during the initialization stage, but during the propagation stage it promoted the reaction. This study demonstrated that MMA can be used to achieve photocurable nanocomposites with homogenously dispersed GBN, and that the presence of GBN significantly modified the polymerization mechanism while an adaptation of the printing parameters is necessary in order to allow the printability of these nanocomposites.
In Vitro and In Vivo Antihypertensive Effect of Milk Fermented with Different Strains of Common Starter Lactic Acid Bacteria
Authors: Glazunova Olga A. , Moiseenko Konstantin V. , Savinova Olga S. , Fedorova Tatyana V.
Published: December 2022

Currently, functional dairy products pave a promising way for the prophylaxis of essential hypertension, and the search for new strains capable of producing such products is a constant challenge for scientists around the world. In this study, the antihypertensive properties of milk fermented with several strains of traditional yogurt starters (Lactobacillus delbrueckii strains Lb100 and Lb200; Lactococcus lactis strains dlA, AM1 and MA1; Streptococcus thermophilus strains 159 and 16t) and one strain of non-conventional probiotic starter (Lacticaseibacillus paracasei ABK) were assessed. The in vitro assessment using angiotensin-converting enzyme inhibition assay was performed for all fermentation products, and the best performed products were tested in vivo using Spontaneously Hypertensive Rat (SHR) animal model. In addition, for the best performed products the fatty acid (FA) composition and FA-related nutritional indices were determined. As a result, the milk fermented with two strains (Lb. delbrueckii LB100 and Lc. lactis AM1) demonstrated significant antihypertensive effect during both in vitro and in vivo experiments. Moreover, the milk fermented with Lb. delbrueckii Lb100 demonstrated significantly better FA-related nutritional indexes and lowered total cholesterol in SHRs upon regular consumption. The obtained results can be used in the future to develop new starter cultures producing effective functional antihypertensive dairy products.
Modeling Obesity-Associated Ovarian Dysfunction in Drosophila
Authors: Liu Huanju , Li Jiajun , Chang Xinyue , He Feng , Ma Jun
Published: December 2022

We perform quantitative studies to investigate the effect of high-calorie diet on Drosophila oogenesis. We use the central composite design (CCD) method to obtain quadratic regression models of body fat and fertility as a function of the concentrations of protein and sucrose, two major macronutrients in Drosophila diet, and treatment duration. Our results reveal complex interactions between sucrose and protein in impacting body fat and fertility when they are considered as an integrated physiological response. We verify the utility of our quantitative modeling approach by experimentally confirming the physiological responses—including increased body fat, reduced fertility, and ovarian insulin insensitivity—expected of a treatment condition identified by our modeling method. Under this treatment condition, we uncover a Drosophila oogenesis phenotype that exhibits an accumulation of immature oocytes and a halt in the production of mature oocytes, a phenotype that bears resemblance to key aspects of the human condition of polycystic ovary syndrome (PCOS). Our analysis of the dynamic progression of different aspects of diet-induced pathophysiology also suggests an order of the onset timing for obesity, ovarian dysfunction, and insulin resistance. Thus, our study documents the utility of quantitative modeling approaches toward understanding the biology of Drosophila female reproduction, in relation to diet-induced obesity and type II diabetes, serving as a potential disease model for human ovarian dysfunction.
Saffron against Neuro-Cognitive Disorders: An Overview of Its Main Bioactive Compounds, Their Metabolic Fate and Potential Mechanisms of Neurological Protection
Authors: Cerdá-Bernad Débora , Costa Leonor , Serra Ana Teresa , Bronze Maria Rosário , Valero-Cases Estefanía , Pérez-Llamas Francisca , Candela María Emilia , Arnao Marino B. , Barberán Francisco Tomás , Villalba Rocío García , García-Conesa María-Teresa , Frutos María-José
Published: December 2022

Saffron (Crocus sativus L.) is a spice used worldwide as a colouring and flavouring agent. Saffron is also a source of multiple bioactive constituents with potential health benefits. Notably, saffron displays consistent beneficial effects against a range of human neurological disorders (depression, anxiety, sleeping alterations). However, the specific compounds and biological mechanisms by which this protection may be achieved have not yet been elucidated. In this review, we have gathered the most updated evidence of the neurological benefits of saffron, as well as the current knowledge on the main saffron constituents, their bioavailability and the potential biological routes and postulated mechanisms by which the beneficial protective effect may occur. Our aim was to provide an overview of the neuroprotective effects attributed to this product and its main bioactive compounds and to highlight the main research gaps that need to be further pursued to achieve full evidence and understanding of the benefits of saffron. Overall, improved clinical trials and adequately designed pre-clinical studies are needed to support the evidence of saffron and of its main bioactive components (e.g., crocin, crocetin) as a therapeutic product to combat neurological disorders.
Association between Fecal Microbiota, SCFA, Gut Integrity Markers and Depressive Symptoms in Patients Treated in the Past with Bariatric Surgery—The Cross-Sectional Study
Authors: Komorniak Natalia , Martynova-Van Kley Alexandra , Nalian Armen , Wroński Michał , Kaseja Krzysztof , Kowalewski Bartosz , Kaźmierczak-Siedlecka Karolina , Łoniewski Igor , Kaczmarczyk Mariusz , Podsiadło Konrad , Bogdański Paweł , Palma Joanna , Stachowska Ewa
Published: December 2022

(1) Background: Depressive symptoms often appear after surgical treatment. (2) Methods: We involved 41 adults who underwent bariatric surgery a minimum of 6 months before the study and had the Beck scale ≥12. We analysed patients’ mental state, gut barrier markers, faecal short chain fatty acids, and microbiota. (3) Results: Gut microbiota composition differed significantly among patients undergoing two different types of surgery (F = 1.64, p = 0.00002). Additionally, we discovered an association between short chain fatty acids and the Beck scale (F = 1.22, p = 0.058). The rearrangement of bacterial metabolites may be due to the patients’ use of increased dietary protein, with insufficient intake of products containing vegetable fiber (Diet Quality Index (DQI-I )adequacy 22.55 (±3.46) points). (4) Conclusions: Bariatric surgery affects the gut microbiota, which may play an important role in the development of depressive and gastrointestinal symptoms in patients after bariatric surgery. Low fiber consumption and increased levels of faecal isobutyric acid may lead to intestinal inflammation. There is a need for further research on this topic including a larger sample size.
Nutrition, Food and Diet in Health and Longevity: We Eat What We Are
Authors: Rattan Suresh I. S. , Kaur Gurcharan
Published: December 2022

Nutrition generally refers to the macro- and micro-nutrients essential for survival, but we do not simply eat nutrition. Instead, we eat animal- and plant-based foods without always being conscious of its nutritional value. Furthermore, various cultural factors influence and shape our taste, preferences, taboos and practices towards preparing and consuming food as a meal and diet. Biogerontological understanding of ageing has identified food as one of the three foundational pillars of health and survival. Here we address the issues of nutrition, food and diet by analyzing the biological importance of macro- and micro-nutrients including hormetins, discussing the health claims for various types of food, and by reviewing the general principles of healthy dietary patterns, including meal timing, caloric restriction, and intermittent fasting. We also present our views about the need for refining our approaches and strategies for future research on nutrition, food and diet by incorporating the molecular, physiological, cultural and personal aspects of this crucial pillar of health, healthy ageing and longevity.
Nutritional Impact and Eating Pattern Changes in Schizophrenic Spectrum Disorders after Health Education Program on Symbiotic Dietary Modulation Offered by Specialised Psychiatric Nursing–Two-Arm Randomised Clinical Trial
Authors: Sevillano-Jiménez Alfonso , Romero-Saldaña Manuel , García-Rodríguez María , Molina-Luque Rafael , Molina-Recio Guillermo
Published: December 2022

Background: The traditional therapeutic approach has perceived the role of nutrition as a minor intervention in psychiatry. The microbiota–gut–brain axis theory evidences the influence of dietary and nutritional patterns on mental health. Aims: To evidence the impact of dietary advice on increasing symbiotic intake on nutritional status and dietary habits in individuals with schizophrenia spectrum disorders. Methods: Randomised clinical trial (two-arm, double-blind, balanced-block, six-month intervention) in 50 individuals diagnosed with schizophrenia spectrum disorders. The control group received conventional dietary advice on an individual basis. A personal nutritional education programme was established in the intervention group (IG) to increase prebiotic and probiotic intake through dietary advice (dairy and fermented foods, green leafy vegetables, high-fibre fruit, whole grains, etc.). Data on nutritional status and dietary habits were collected (baseline and six months). The degree of dietary adherence to the recommended patterns was recorded weekly. Anthropometric parameters were also analysed monthly. Results: Finally, 44 subjects completed the follow-up. All participants exceeded the dietary reference intakes. The overall and intra-group analysis showed a statistically significant (p < 0.05) reduction in macro and micronutrient intakes with a closer approximation to the recommended dietary intakes, except for polyunsaturated fatty acids, oligosaccharides, polysaccharides and dietary fibre. After six months of intervention, statistical differences (p < 0.001) were found in all variables of the anthropometric profile in the IG, as well as an increase in the consumption of foods with a high symbiotic content (at baseline and six months). Likewise, a reduction in eggs, meat, fish, sugars and ultra-processed foods was evident, leading to significant intra-group differences (p < 0.05). Conclusions: Implementing conventional nutritional education strategies and specific nutritional advice with a symbiotic effect improves the dietary-nutritional profile in patients with schizophrenia spectrum disorders. Furthermore, it highlights the nutritional impact on mental health, stating itself as adjuvant therapy for physical health and lifestyle improvement.
Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke
Authors: Zhou Rong , Lin Kuan , Leng Changlong , Zhou Mei , Zhang Jing , Li Youwei , Liu Yujing , Ye Xiansheng , Xu Xiaoli , Sun Binlian , Shu Xiji , Liu Wei
Published: December 2022

Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from Terminalia chebula has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans.
The Effect of Breast Milk Microbiota on the Composition of Infant Gut Microbiota: A Cohort Study
Authors: Li Yapeng , Ren Lei , Wang Yunyi , Li Jinxing , Zhou Qingqing , Peng Chenrui , Li Yuchen , Cheng Ruyue , He Fang , Shen Xi
Published: December 2022

Evidence shows that breast milk microbiota and an infant’s gut microbiota are related. This study aimed to compare the effects of breast milk microbiota on the construction and colonization of gut microbiota in newborns. In this study, 23 healthy infants were selected and divided into a breastfeeding group (13) and a mixed feeding group (10) based on the feeding method within one month of age. Infant fecal and breast milk samples were collected on the day of birth (0 day) and 30 days after birth (30 days) for 16S rRNA second-generation sequencing and SCFA detection. The results showed that Firmicutes and Actinobacteriota on day 0 and Firmicutes and Proteobacteria on 30 d dominated breast milk gut microbiota. There were correlations between the breast milk microbiota and the infant gut microbiota in each group (p < 0.05). Additionally, breast milk microbiota correlated more significantly with infants’ SCFAs in the breastfeeding group than in the mixed feeding group. This study showed that breast milk microbiota partially influences the construction of infant gut microbiota, with some key strains having a crucial influence, such as Lactobacillus, Bifidobacterium, and Enterobacter. However, the effect of breast milk microbiota on infant gut microbiota is not through direct strain transmission but has been indirectly influenced, which may be related to the cross-feeding effect mediated by SCFAs.
Maternal Gliadin Intake Reduces Oocyte Quality with Chromosomal Aberrations and Increases Embryonic Lethality through Oxidative Stress in a Caenorhabditis elegans Model
Authors: Lee Jae Hyuck , Lee Mijin , Min Hyemin , Youn Esther , Shim Yhong-Hee
Published: December 2022

Oocyte quality is essential for reproductive capacity, but it rapidly declines with age. In addition to aging, maternal nutrition is a major concern in maintaining oocyte quality. Gliadin, a major component of gluten, causes gluten toxicity, which has been reported in a variety of gluten-related disorders. The basis of gluten toxicity in reproduction is being understood using simple animal models such as Caenorhabditis elegans. In this study, we examined the effects of gliadin peptide (GP; amino acids 151–170) intake on oocyte quality control in C. elegans. We found that GP intake impaired oocyte quality through chromosomal aberrations and mitochondrial oxidative stress, which was suppressed by antioxidant treatment. The reduced oocyte quality by GP intake consequently increased embryonic lethality. Furthermore, the expression of oxidative stress-responding genes prdx-3 and gst-4 was significantly increased by GP intake. The increased DAF-16 activity by GP intake suggests that DAF-16 is a possible transactivator of these antioxidant genes. Taken together, GP intake reduced reproductive capacity in C. elegans by decreasing oocyte quality and increasing embryonic lethality through mitochondrial oxidative stress.
Quality of Nursing Work Life among Nurses in Saudi Arabia: A Descriptive Cross-Sectional Study
Authors: Al Mutair Abbas , Al Bazroun Mohammed I. , Almusalami Eman M. , Aljarameez Faiza , Alhasawi Amal I. , Alahmed Fatimah , Saha Chandni , Alharbi Hanan F. , Ahmed Gasmelseed Y.
Published: December 2022

Background: Quality of working life (QWL) is a multidimensional concept that describes an employee’s satisfaction with several work life elements. Quality of nurse working life is considered as a stepping stone for health services improvement, as it affects job satisfaction which, in turn, affects the performance of nurses. Understanding and investigating the nurses’ quality of work life in Saudi Arabia is needed for improvement actions. Objectives: This study aimed to examine the quality of nursing work life (QNWL) among nurses working in Saudi Arabia and to determine the association between demographic variables and quality of work life among nurses. Methods: It was a cross-sectional design using Brooks’ quality of nursing work life survey. It was distributed among nurses over the kingdom of Saudi Arabia. Results: There were 860 nurses participating in the study. The mean total score for the participants was 174.5+/− 30.3, indicating moderate to high QNWL. The highest score achieved by the nurses was for the work world context (4.29) while the lowest score was for work design dimension (3.92). The study revealed that nationality, income, and shift duration, having a dependent person, and having family accompany the nurse as significant factors affecting the quality of work life among the nurses. Conclusion: A novel contribution of the current study was that the demographic characteristics of the participants, including nationality, income, having family accompany the nurse, having an independent child, or spouse or parents, and shift duration, tended to have a statistically significant correlation with QNWL. The comprehensive results of this study have practical implications whereby authority bodies can create regulatory plans for enhancing satisfaction and performance over the sole utilization of job satisfaction measurements and can thereby improve nurses’ retention and turnover rates.
Differential Role of Type 2 Diabetes as a Risk Factor for Tuberculosis in the Elderly versus Younger Adults
Authors: Restrepo Blanca I. , Scordo Julia M. , Aguillón-Durán Génesis P. , Ayala Doris , Quirino-Cerrillo Ana Paulina , Loera-Salazar Raúl , Cruz-González America , Caso Jose A. , Joya-Ayala Mateo , García-Oropesa Esperanza M. , Salinas Alejandra B. , Martinez Leonardo , Schlesinger Larry S. , Torrelles Jordi B. , Turner Joanne
Published: December 2022

The elderly are understudied despite their high risk of tuberculosis (TB). We sought to identify factors underlying the lack of an association between TB and type 2 diabetes (T2D) in the elderly, but not adults. We conducted a case–control study in elderly (≥65 years old; ELD) vs. younger adults (young/middle-aged adults (18–44/45–64 years old; YA|MAA) stratified by TB and T2D, using a research study population (n = 1160) and TB surveillance data (n = 8783). In the research study population the adjusted odds ratio (AOR) of TB in T2D was highest in young adults (AOR 6.48) but waned with age becoming non-significant in the elderly. Findings were validated using TB surveillance data. T2D in the elderly (vs. T2D in younger individuals) was characterized by better glucose control (e.g., lower hyperglycemia or HbA1c), lower insulin resistance, more sulphonylureas use, and features of less inflammation (e.g., lower obesity, neutrophils, platelets, anti-inflammatory use). We posit that differences underlying glucose dysregulation and inflammation in elderly vs. younger adults with T2D, contribute to their differential association with TB. Studies in the elderly provide valuable insights into TB-T2D pathogenesis, e.g., here we identified insulin resistance as a novel candidate mechanism by which T2D may increase active TB risk.
Evolution of Rabies Virus Isolates: Virulence Signatures and Effects of Modulation by Neutralizing Antibodies
Authors: Conselheiro Juliana Amorim , Barone Gisely Toledo , Miyagi Sueli Akemi Taniwaki , de Souza Silva Sheila Oliveira , Agostinho Washington Carlos , Aguiar Joana , Brandão Paulo Eduardo
Published: December 2022

Lyssavirus rabies (RABV) is an RNA virus and, therefore, is subject to mutations due to low RNA polymerase replication fidelity, forming a population structure known as a viral quasispecies, which is the core of RNA viruses’ adaptive strategy. Under new microenvironmental conditions, the fittest populations are selected, and the study of this process on the molecular level can help determine molecular signatures related to virulence. Our aim was to survey gene signatures on nucleoprotein and glycoprotein genes that might be involved in virulence modulation during the in vitro evolution of RABV lineages after serial passages in a neuronal cell system with or without the presence of neutralizing antibodies based on replicative fitness, in vivo neurotropism and protein structure and dynamics. The experiments revealed that amino acids at positions 186 and 188 of the glycoprotein are virulence factors of Lyssavirus rabies, and site 186 specifically might allow the attachment to heparan as a secondary cell receptor, while polymorphism at position 333 might allow the selection of escape mutants under suboptimal neutralizing antibodies titers.
Antidiabetic Potential of Novel 1,3,5-Trisubstituted-2-Thioxoimidazloidin-4-One Analogues: Insights into α-Glucosidase, α-Amylase, and Antioxidant Activities
Authors: Khirallah Salma M. , Ramadan Heba M. M. , Aladl Hossam Aladl Aladl , Ayaz Najla O. , Kurdi Lina A. F. , Jaremko Mariusz , Alshawwa Samar Zuhair , Saied Essa M.
Published: December 2022

As the ninth leading cause of death globally, diabetes mellitus (DM) is considered to be the worst chronic metabolic disease requiring an enormous need for healthcare with over 578 million expected cases by 2023. Several recent findings have demonstrated that mediating the activity of carbohydrate-hydrolyzing enzymes, including α-amylase and α-glucosidase, could be a potential strategy for managing the development of DM. In the presented study, a novel set of 1,3,5-trisubstituted-2-thioxoimidazolidin-4-ones was designed, synthesized, and characterized. The antidiabetic activity of the synthesized compounds was explored by assessing their inhibitory activity toward α-amylase and α-glucosidase enzymes. The results demonstrated that this class of compounds exhibits considerable inhibitory activity toward both α-amylase and α-glucosidase enzymes. Among the synthesized compounds, compound 5a demonstrated the most inhibitory activity with IC50 of 5.08 and µg/mL and 0.21 µg/mL toward α-glucosidase and α-amylase activities, respectively, as compared to the drug Acarbose (IC50 = 5.76 µg/mL and 0.39 µg/mL, respectively). To gain insights into the antidiabetic potential of compound 5a, we assessed the cytotoxic and antioxidant activities. Our findings indicated that compound 5a displays considerable cytotoxicity toward WI-38 cells with an IC50 of 88.54 µg/mL, as compared to the drug Celecoxib (IC50 = 93.05 µg/mL). Further, compound 5a exhibited a high scavenging activity toward 2,2-Diphenyl1-picrylhydrazyl (DPPH) free radicals (IC50 = 51.75 µg/mL) and showed a low potential to produce ROS as indicated by the monitoring of the generated H2O2 (132.4 pg/mL), as compared to Trolox (IC50 = 58.09 µg/mL) and Celecoxib (171.6 pg/mL). Finally, we performed extensive molecular modeling studies to affirm the binding affinity of this class of compounds to the binding pocket of α-amylase and α-glucosidase enzymes. Collectively, our findings indicate that this class of compounds, particularly compound 5a, could be utilized as a lead structure for the development of novel compounds with potential antidiabetic and antioxidant activities.
Heart Uptake of [18F]Fluoro-4-Thia-Oleate in a Non-Alcoholic Fatty Liver Disease Mouse Model
Authors: Li Junfeng , Hu Weidong , Peng Jiangling , Wong Patty , Kandeel Fouad , Olafsen Tove , Shively John E.
Published: December 2022

The world-wide high incidence of non-alcoholic fatty liver disease (NAFLD) is of concern for its progression to insulin resistance, steatohepatitis and cardiovascular disease (CVD). The increased uptake of fatty acids in critical organs plays a major role in NAFLD progression. Male Ceacam1−/− mice that develop NAFLD, insulin resistance and CVD on normal chow are a potential model for studying the dysregulation of fatty acid uptake. [18F]fluoro-4-thia-oleate ([18F]FTO) was chosen as a fatty acid reporter because of its higher uptake and retention in the heart in an animal model of CVD. Male wild-type (WT) or Ceacam1−/− mice fasted 4–6 h were administered [18F]FTO i.v., and dynamic PET scans were conducted in an MR/PET small animal imaging system along with terminal tissue biodistributions. Quantitative heart image analysis revealed significantly higher uptake at 35 min in Ceacam1−/− (6.0 ± 1.0% ID/cc) vs. WT (3.9 ± 0.6% ID/cc) mice (p = 0.006). Ex vivo heart uptake/retention (% ID/organ) was 2.82 ± 0.45 for Ceacam1−/− mice vs. 1.66 ± 0.45 for WT mice (p < 0.01). Higher kidney and pancreas uptake/retention in Ceacam1−/− was also evident, and the excretion of [18F]FTO into the duodenum was observed for both WT and Ceacam1−/− mice starting at 10 min. This study suggests that the administration of [18F]FTO as a marker of fatty acid uptake and retention may be an important tool in analyzing the effect of NAFLD on lipid dysregulation in the heart.
Nanoparticles Obtained from Zein for Encapsulation of Mesalazine
Authors: Lima Izabela Borges C. , Moreno Lina Clara G. A. I. , Peres Ana Victória , Santana Ana Cristina Gramoza , Carvalho Adonias , Chaves Mariana H. , Lima Lorena , Sousa Rayran Walter , Dittz Dalton , Rolim Hercília M. L. , Nunes Lívio César Cunha
Published: December 2022

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of −36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas–Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer–Peppas model with the Fickian release mechanism, or “Case I”. An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route.
Comparison of the Formulation, Stability and Biological Effects of Hydrophilic Extracts from Black Elder Flowers (Sambucus nigra L.)
Authors: Laurutis Aurelijus , Liobikas Julius , Stanciauskaite Monika , Marksa Mindaugas , Ramanauskiene Kristina , Majiene Daiva
Published: December 2022

Elderflower preparations have long been used to treat colds and flu, but their use is undeservedly reduced, and only dried flower teas, less often ethanolic extracts, can be purchased in pharmacies. In the case of homemade teas, the medicinal plant material is extracted with hot water for a relatively short time, thus only a small part of the active substances is extracted. The industrially produced ethanolic extract is rich in active substances, but its use is limited since ethanol in many countries is undesirable and unsuitable for children and geriatric patients. Therefore, the aim of this work was to produce extracts from elder flowers using water as extractant and a mixture of water + polyethylene glycol (PEG) 20%, to compare their chemical composition and stability, and to study the ability to neutralize reactive oxygen species (ROS) and to sustain the viability of C6 glial cells under oxidative stress conditions. The ethanolic extract was used as a standard. Thus, the extract with PEG contained more than two times higher amount of total phenolics (PC) than the aqueous one, and the stability at 6–8 °C was comparable to the stability of ethanolic extract. All three extracts showed an antioxidant effect in a concentration-dependent manner in vitro. However, only the PEG containing extract (at 20–40 µg/mL PC) was the most effective in reducing the intracellular level of ROS and sustaining the viability of glial cells. The results suggest that the co-solvent PEG increases the yield of phenolics in the extract, prolongs the stability, and enhances positive biological effects.
Clay-Based Hydrogels as Drug Delivery Vehicles of Curcumin Nanocrystals for Topical Application
Authors: Ruggeri Marco , Sánchez-Espejo Rita , Casula Luca , Barbosa Raquel de Melo , Sandri Giuseppina , Cardia Maria Cristina , Lai Francesco , Viseras César
Published: December 2022

The poor water solubility of a significant number of active pharmaceutical ingredients (API) remains one of the main challenges in the drug development process, causing low bioavailability and therapeutic failure of drug candidates. Curcumin is a well-known Biopharmaceutics Classification System (BCS) class IV drug, characterized by lipophilicity and low permeability, which hampers topical bioavailability. Given these premises, the aim of this work was the design and the development of curcumin nanocrystals and their incorporation into natural inorganic hydrogels for topical application. Curcumin nanocrystals were manufactured by the wet ball milling technique and then loaded in clay-based hydrogels. Bentonite and/or palygorskite were selected as the inorganic gelling agents. Curcumin nanocrystal-loaded hydrogels were manufactured by means of a homogenization process and characterized with respect to their chemico-physical properties, in vitro release, antioxidant activity and skin permeation. The results highlighted that the presence of bentonite provided an increase of curcumin skin penetration and simultaneously allowed its radical scavenging properties, due to the desirable rheological characteristics, which should guarantee the necessary contact time of the gel with the skin.
Predicting the Temperature Evolution during Nanomilling of Drug Suspensions via a Semi-Theoretical Lumped-Parameter Model
Authors: Guner Gulenay , Yilmaz Dogacan , Yao Helen F. , Clancy Donald J. , Bilgili Ecevit
Published: December 2022

Although temperature can significantly affect the stability and degradation of drug nanosuspensions, temperature evolution during the production of drug nanoparticles via wet stirred media milling, also known as nanomilling, has not been studied extensively. This study aims to establish both descriptive and predictive capabilities of a semi-theoretical lumped parameter model (LPM) for temperature evolution. In the experiments, the mill was operated at various stirrer speeds, bead loadings, and bead sizes, while the temperature evolution at the mill outlet was recorded. The LPM was formulated and fitted to the experimental temperature profiles in the training runs, and its parameters, i.e., the apparent heat generation rate Qgen and the apparent overall heat transfer coefficient times surface area UA, were estimated. For the test runs, these parameters were predicted as a function of the process parameters via a power law (PL) model and machine learning (ML) model. The LPM augmented with the PL and ML models was used to predict the temperature evolution in the test runs. The LPM predictions were also compared with those of an enthalpy balance model (EBM) developed recently. The LPM had a fitting capability with a root-mean-squared error (RMSE) lower than 0.9 °C, and a prediction capability, when augmented with the PL and ML models, with an RMSE lower than 4.1 and 2.1 °C, respectively. Overall, the LPM augmented with the PL model had both good descriptive and predictive capability, whereas the one with the ML model had a comparable predictive capability. Despite being simple, with two parameters and obviating the need for sophisticated numerical techniques for its solution, the semi-theoretical LPM generally predicts the temperature evolution similarly or slightly better than the EBM. Hence, this study has provided a validated, simple model for pharmaceutical engineers to simulate the temperature evolution during the nanomilling process, which will help to set proper process controls for thermally labile drugs.
A Thermosensitive, Chitosan-Based Hydrogel as Delivery System for Antibacterial Liposomes to Surgical Site Infections
Authors: Kaul Laurine , Grundmann Clara E. , Köll-Weber Monika , Löffler Hanna , Weiz Artur , Zannettino Andrew C. W. , Richter Katharina , Süss Regine
Published: December 2022

Prophylaxis and the treatment of surgical site infections (SSIs) with antibiotics frequently fail due to the antibiotic resistance of bacteria and the ability of bacteria to reside in biofilms (i.e., bacterial clusters in a protective matrix). Therefore, alternative antibacterial treatments are required to combat biofilm infections. The combination of diethyldithiocarbamate (DDC−) and copper ions (Cu2+) exhibited antibiofilm activity against the staphylococci species associated with SSIs; however, the formation of a water-insoluble Cu(DDC)2 complex limits its application to SSIs. Here, we describe the development and antibiofilm activity of an injectable gel containing a liposomal formulation of Cu(DDC)2 and Cu2+ (lipogel). Lyophilized liposomes were incorporated into a mixture of chitosan (CS) and beta-glycerophosphate (βGP), and the thermosensitive gelling properties of CS-βGP and the lipogel were determined. The liposomes remained stable after lyophilization over six months at 4–6 °C and −20 °C. The sol-gel transition of the gel and lipogel occurred between 33 and 39 °C, independently of sterilization or storage at −20 °C. CS-βGP is biocompatible and the liposomes were released over time. The lipogel prevented biofilm formation over 2 days and killed 98.7% of the methicillin-resistant Staphylococcus aureus and 99.9% of the Staphylococcus epidermidis biofilms. Therefore, the lipogel is a promising new prophylaxis and treatment strategy for local application to SSIs.
Effects of Mangiferin on LPS-Induced Inflammation and SARS-CoV-2 Viral Adsorption in Human Lung Cells
Authors: Spampinato Mariarita , Carota Giuseppe , Sferrazzo Giuseppe , Fuochi Virginia , Distefano Alfio , Ronsisvalle Simone , Sipala Federica , Giuffrida Rosario , Furneri Pio Maria , Di Rosa Michelino , Tibullo Daniele , Li Volti Giovanni , Barbagallo Ignazio
Published: December 2022

The growing interest in natural bioactive molecules, as an approach to many pathological contexts, is widely justified by the necessity to overcome the disadvantageous benefit–risk ratio related to traditional therapies. Among them, mangiferin (MGF) shows promising beneficial properties such as antioxidant, anti-inflammatory, and immunomodulatory effects. In this study, we aimed to investigate the antioxidant and anti-inflammatory properties of MGF on lipopolysaccharide (LPS)-induced lung NCI-H292 cells, focusing on its role against COVID-19 adsorption. In order to obtain this information, cells treated with LPS, with or without MGF, were analyzed performing wound healing, gene expression of inflammatory cytokines, GSH quantification, and JC-1 staining. Moreover, the inhibition of viral adsorption was evaluated microbiologically and the results were further confirmed by molecular docking analysis. In this regard, MGF downregulates the expression of several inflammatory factors, enhances GSH levels, promotes the wound healing rate, and restores the mitochondrial dysfunction caused by LPS. In addition, MGF significantly inhibits SARS-CoV-2 adsorption as shown by the gene expression of ACE2 and TMPRSS-2, and furtherly confirmed by microbiological and molecular modeling evaluation. Although more investigations are still needed, all data obtained constitute a solid background, demonstrating the cytoprotective role of MGF in inflammatory mechanisms including COVID-19 infection.
Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes
Authors: Vasilieva Elmira A. , Kuznetsova Darya A. , Valeeva Farida G. , Kuznetsov Denis M. , Zakharov Andrey V. , Amerhanova Syumbelya K. , Voloshina Alexandra D. , Zueva Irina V. , Petrov Konstantin A. , Zakharova Lucia Ya.
Published: December 2022

Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from −15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%.