bluuebunny/crossref_metadata_2025 huggingface dataset:
Silver Nanoparticles Formation by Jatropha integerrima and LC/MS-QTOF-Based Metabolite Profiling
Authors: Mohammed Afrah E. , Al-Keridis Lamya Ahmed , Rahman Ishrat , Alotaibi Modhi O. , Suliman Rasha Saad , Alrajhi Aisha Mohammed , Elobeid Mudawi M. , Alothman Monerah R. , Alhomaidi Eman A. , Korany Shereen M.
Published: September 2021

The broad application of metal nanoparticles in different fields encourages scientists to find alternatives to conventional synthesis methods to reduce negative environmental impacts. Herein, we described a safe method for preparing silver nanoparticles (J-AgNPs) using Jatropha integerrima leaves extract as a reducing agent and further characterize its physiochemical and pharmacological properties to identify its therapeutic potential as a cytotoxic and antimicrobial agent. The biogenic synthesized J-AgNPs were physiochemically characterized by ultraviolet-visible spectroscopy, dynamic light scattering (DLS), transmission electron microscope (TEM), and energy-dispersive X-ray spectroscopy. HPLC-DAD, followed by LC/MS and the Fourier-transform infrared spectroscopy (FTIR), was applied to detect the biomolecules of J. integerrima involved in the fabrication of NPs. Furthermore, J-AgNPs and the ampicillin-nanocomposite conjugate were investigated for their potential antibacterial effects against four clinical isolates. Finally, cytotoxic effects were also investigated against cancer and normal cell lines, and their mechanism was assessed using TEM analysis and confocal laser scanning microscopy (LSM). Ag ions were reduced to spherical J-AgNPs, with a zeta potential of −34.7 mV as well as an average size of 91.2 and 22.8 nm as detected by DLS and TEM, respectively. HPLC GC/MC analysis identified five biomolecules, and FTIR suggested the presence of proteins besides polyphenolic molecules; together, these molecules could be responsible for the reduction and capping processes during NP formation. Additionally, J-AgNPs displayed a strong antibacterial effect, although the ampicillin conjugated form had a very weak antibacterial effect. Furthermore, the NPs caused a reduction in cell viability of all the treated cells by initiating ultrastructural changes and apoptosis, as identified by TEM and LSM analysis. Therefore, J-AgNPs can be formed using the leaf extract from the J. integerrima plant. Furthermore, J-AgNPs may serve as a candidate for further biochemical and pharmacological testing to identify its therapeutic value.
The Construction of Multi-Incorporated Polylactic Composite Nanofibrous Scaffold for the Potential Applications in Bone Tissue Regeneration
Authors: Nie Du , Luo Yi , Li Guang , Jin Junhong , Yang Shenglin , Li Suying , Zhang Yu , Dai Jiamu , Liu Rong , Zhang Wei
Published: September 2021

To improve the bone regeneration ability of pure polymer, varieties of bioactive components were incorporated to a biomolecular scaffold with different structures. In this study, polysilsesquioxane (POSS), pearl powder and dexamethasone loaded porous carbon nanofibers (DEX@PCNFs) were incorporated into polylactic (PLA) nanofibrous scaffold via electrospinning for the application of bone tissue regeneration. The morphology observation showed that the nanofibers were well formed through electrospinning process. The mineralization test of incubation in simulated body fluid (SBF) revealed that POSS incorporated scaffold obtained faster hydroxyapatite depositing ability than pristine PLA nanofibers. Importantly, benefitting from the bioactive components of pearl powder like bone morphogenetic protein (BMP), bone mesenchymal stem cells (BMSCs) cultured on the composite scaffold presented higher proliferation rate. In addition, by further incorporating with DEX@PCNFs, the alkaline phosphatase (ALP) level and calcium deposition were a little higher based on pearl powder. Consequently, the novel POSS, pearl powder and DEX@PCNFs multi-incorporated PLA nanofibrous scaffold can provide better ability to enhance the biocompatibility and accelerate osteogenic differentiation of BMSCs, which has potential applications in bone tissue regeneration.
Synthesis and Characterization of Cu2ZnSnS4 Thin Films Obtained by Combined Magnetron Sputtering and Pulsed Laser Deposition
Authors: Zaki Mohamed-Yassine , Sava Florinel , Buruiana Angel-Theodor , Simandan Iosif-Daniel , Becherescu Nicu , Galca Aurelian-Catalin , Mihai Claudia , Velea Alin
Published: September 2021

Cu2ZnSnS4 (CZTS) is a complex quaternary material, and obtaining a single-phase CZTS with no secondary phases is known to be challenging and dependent on the production technique. This work involves the synthesis and characterization of CZTS absorber layers for solar cells. Thin films were deposited on Si and glass substrates by a combined magnetron sputtering (MS) and pulsed laser deposition (PLD) hybrid system, followed by annealing without and with sulfur powder at 500 °C under argon (Ar) flow. Three different Cu2S, SnS2, and ZnS targets were used each time, employing a different target for PLD and the two others for MS. The effect of the different target arrangements and the role of annealing and/or sulfurization treatment were investigated. The characterization of the absorber films was performed by grazing incidence X-ray diffraction (GIXRD), X-ray reflectometry (XRR), Raman spectroscopy, scanning electron microscopy, and regular transmission spectroscopy. The film with ZnS deposited by PLD and SnS2 and Cu2S by MS was found to be the best for obtaining a single CZTS phase, with uniform surface morphology, a nearly stoichiometric composition, and an optimal band gap of 1.40 eV. These results show that a new method that combines the advantages of both MS and PLD techniques was successfully used to obtain single-phase Cu2ZnSnS4 films for solar cell applications.
BiVO4 Ceramic Photoanode with Enhanced Photoelectrochemical Stability
Authors: Zheng Liren , Wang Minrui , Li Yujie , Ma Fahao , Li Jiyu , Jiang Weiyi , Liu Mu , Cheng Hefeng , Wang Zeyan , Zheng Zhaoke , Wang Peng , Liu Yuanyuan , Dai Ying , Huang Baibiao
Published: September 2021

Monoclinic bismuth vanadate (BiVO4) is an attractive material with which to fabricate photoanodes due to its suitable band structure and excellent photoelectrochemical (PEC) performance. However, the poor PEC stability originating from its severe photo-corrosion greatly restricts its practical applications. In this paper, pristine and Mo doped BiVO4 ceramics were prepared using the spark plasma sintering (SPS) method, and their photoelectrochemical properties as photoanodes were investigated. The as-prepared 1% Mo doped BiVO4 ceramic (Mo-BVO (C)) photoanode exhibited enhanced PEC stability compared to 1% Mo doped BiVO4 films on fluorine doped Tin Oxide (FTO) coated glass substrates (Mo-BVO). Mo-BVO (C) exhibited a photocurrent density of 0.54 mA/cm2 and remained stable for 10 h at 1.23 V vs. reversible hydrogen electrode (RHE), while the photocurrent density of the Mo-BVO decreased from 0.66 mA/cm2 to 0.11 mA/cm2 at 1.23 V vs. RHE in 4 h. The experimental results indicated that the enhanced PEC stability of the Mo-BVO (C) could be attributed to its higher crystallinity, which could effectively inhibit the dissociation of vanadium in BiVO4 during the PEC process. This work may illustrate a novel ceramic design for the improvement of the stability of BiVO4 photoanodes, and might provide a general strategy for the improvement of the PEC stability of metal oxide photoanodes.
Synthesis and In Vitro Evaluation of Gold Nanoparticles Functionalized with Thiol Ligands for Robust Radiolabeling with 99mTc
Authors: Apostolopoulou Adamantia , Chiotellis Aristeidis , Salvanou Evangelia-Alexandra , Makrypidi Konstantina , Tsoukalas Charalampos , Kapiris Fotis , Paravatou-Petsotas Maria , Papadopoulos Minas , Pirmettis Ioannis C. , Koźmiński Przemysław , Bouziotis Penelope
Published: September 2021

Radiolabeled gold nanoparticles (AuNPs) have been widely used for cancer diagnosis and therapy over recent decades. In this study, we focused on the development and in vitro evaluation of four new Au nanoconjugates radiolabeled with technetium-99m (99mTc) via thiol-bearing ligands attached to the NP surface. More specifically, AuNPs of two different sizes (2 nm and 20 nm, referred to as Au(2) and Au(20), respectively) were functionalized with two bifunctional thiol ligands (referred to as L1H and L2H). The shape, size, and morphology of both bare and ligand-bearing AuNPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. In vitro cytotoxicity was assessed in 4T1 murine mammary cancer cells. The AuNPs were successfully radiolabeled with 99mTc-carbonyls at high radiochemical purity (>95%) and showed excellent in vitro stability in competition studies with cysteine and histidine. Moreover, lipophilicity studies were performed in order to determine the lipophilicity of the radiolabeled conjugates, while a hemolysis assay was performed to investigate the biocompatibility of the bare and functionalized AuNPs. We have shown that the functionalized AuNPs developed in this study lead to stable radiolabeled nanoconstructs with the potential to be applied in multimodality imaging or for in vivo tracking of drug-carrying AuNPs.
Valid Statements by the Crowd: Statistical Measures for Precision in Crowdsourced Mobile Measurements
Authors: Wamser Florian , Seufert Anika , Hall Andrew , Wunderer Stefan , Hoßfeld Tobias
Published: September 2021

Crowdsourced network measurements (CNMs) are becoming increasingly popular as they assess the performance of a mobile network from the end user’s perspective on a large scale. Here, network measurements are performed directly on the end-users’ devices, thus taking advantage of the real-world conditions end-users encounter. However, this type of uncontrolled measurement raises questions about its validity and reliability. The problem lies in the nature of this type of data collection. In CNMs, mobile network subscribers are involved to a large extent in the measurement process, and collect data themselves for the operator. The collection of data on user devices in arbitrary locations and at uncontrolled times requires means to ensure validity and reliability. To address this issue, our paper defines concepts and guidelines for analyzing the precision of CNMs; specifically, the number of measurements required to make valid statements. In addition to the formal definition of the aspect, we illustrate the problem and use an extensive sample data set to show possible assessment approaches. This data set consists of more than 20.4 million crowdsourced mobile measurements from across France, measured by a commercial data provider.
Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults
Authors: Richer Stuart , Novil Steven , Gullett Taylor , Dervishi Avni , Nassiri Sherwin , Duong Co , Davis Robert , Davey Pinakin Gunvant
Published: September 2021

Twilight and low luminance levels are visually challenging environments for the elderly, especially when driving at night. Carotenoid rich diets are known to increase macular pigment optical density (MPOD), which in turn leads to an improvement in visual function. It is not known whether augmenting MPOD can lead to a decrease in vision related night driving difficulties. Additionally, it is unknown if carotenoid supplementation provides additional measurable benefits to one’s useful field of view (UFOV) along with a decreased composite crash risk score. The aim of the study was to evaluate changes in night vision function and UFOV in individuals that took carotenoid vitamin supplements for a six-month period compared to a placebo group. Methods: A prospective, randomized, double-blind, six-month trial of a 14 mg zeaxanthin/7 mg lutein-based supplement was carried out. Participants were randomized into active or placebo group (approx 2:1). Results: n = 33 participants (26 males/7 females) participated with 93% capsule intake compliance in the supplemented group (n = 24) and placebo group (n = 9). MPOD (mean/standard error SE) in the active group increased in the Right eye from 0.35 density units (du)/0.04 SE to 0.41 du/0.05 SE; p < 0.001 and in the Left eye from 0.35 du/0.05 SE to 0.37 du, p > 0.05). The supplemented group showed significant improvements in contrast sensitivity with glare in both eyes with improvements in LogMAR scores of 0.147 and 0.149, respectively (p = 0.02 and 0.01, respectively), monocularly tested glare recovery time improved 2.76 and 2.54 s, respectively, (p = 0.008 and p = 0.02), and we also noted a decreased preferred luminance required to complete visual tasks (p = 0.02 and 0.03). Improvements in UFOV scores of divided attention (p < 0.001) and improved composite crash risk score (p = 0.004) were seen in the supplemented group. The placebo group remained unchanged. Conclusions: The NVC demonstrates that augmenting MPOD in individuals with difficulty in night vision showed measurable benefits in numerous visual functions that are important for night vision driving in this small sample RCT. Additionally, we observed an improvement in UFOV divided attention test scores and decreased composite risk scores.
The Effect of Probiotics (MCP® BCMC® Strains) on Hepatic Steatosis, Small Intestinal Mucosal Immune Function, and Intestinal Barrier in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Mohamad Nor Mohamad Hizami , Ayob Nurainina , Mokhtar Norfilza M. , Raja Ali Raja Affendi , Tan Geok Chin , Wong Zhiqin , Shafiee Nor Hamizah , Wong Yin Ping , Mustangin Muaatamarulain , Nawawi Khairul Najmi Muhammad
Published: September 2021

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut–liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP® BCMC® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: −21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: −10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: −0.25 ± 1.77 kPa, p = 0.55 vs. placebo: −0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: −0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (−7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = −2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.
Identifying Nutrient Patterns in South African Foods to Support National Nutrition Guidelines and Policies
Authors: Balakrishna Yusentha , Manda Samuel , Mwambi Henry , van Graan Averalda
Published: September 2021

Food composition databases (FCDBs) provide the nutritional content of foods and are essential for developing nutrition guidance and effective intervention programs to improve nutrition of a population. In public and nutritional health research studies, FCDBs are used in the estimation of nutrient intake profiles at the population levels. However, such studies investigating nutrient co-occurrence and profile patterns within the African context are very rare. This study aimed to identify nutrient co-occurrence patterns within the South African FCDB (SAFCDB). A principal component analysis (PCA) was applied to 28 nutrients and 971 foods in the South African FCDB to determine compositionally similar food items. A second principal component analysis was applied to the food items for validation. Eight nutrient patterns (NPs) explaining 73.4% of the nutrient variation among foods were identified: (1) high magnesium and manganese; (2) high copper and vitamin B12; (3) high animal protein, niacin, and vitamin B6; (4) high fatty acids and vitamin E; (5) high calcium, phosphorous and sodium; (6) low moisture and high available carbohydrate; (7) high cholesterol and vitamin D; and (8) low zinc and high vitamin C. Similar food patterns (FPs) were identified from a PCA on food items, yielding subgroups such as dark-green, leafy vegetables and, orange-coloured fruit and vegetables. One food pattern was associated with high sodium levels and contained bread, processed meat and seafood, canned vegetables, and sauces. The data-driven nutrient and food patterns found in this study were consistent with and support the South African food-based dietary guidelines and the national salt regulations.
An Innovative Machine Learning Approach to Predict the Dietary Fiber Content of Packaged Foods
Authors: Davies Tazman , Louie Jimmy Chun Yu , Scapin Tailane , Pettigrew Simone , Wu Jason HY , Marklund Matti , Coyle Daisy H.
Published: September 2021

Underconsumption of dietary fiber is prevalent worldwide and is associated with multiple adverse health conditions. Despite the importance of fiber, the labeling of fiber content on packaged foods and beverages is voluntary in most countries, making it challenging for consumers and policy makers to monitor fiber consumption. Here, we developed a machine learning approach for automated and systematic prediction of fiber content using nutrient information commonly available on packaged products. An Australian packaged food dataset with known fiber content information was divided into training (n = 8986) and test datasets (n = 2455). Utilization of a k-nearest neighbors machine learning algorithm explained a greater proportion of variance in fiber content than an existing manual fiber prediction approach (R2 = 0.84 vs. R2 = 0.68). Our findings highlight the opportunity to use machine learning to efficiently predict the fiber content of packaged products on a large scale.
An Online Cross-Sectional Survey of Complementary Feeding Practices during the COVID-19 Restrictions in Poland
Authors: Horvath Andrea , Stróżyk Agata , Dziechciarz Piotr , Szajewska Hania
Published: September 2021

This cross-sectional online survey performed in Poland aimed to improve understanding of how COVID-19 pandemic restrictions affected complementary feeding practices among parents of infants aged 4 to 12 months. Self-selected parents were recruited through the internet. The anonymous questionnaire was opened during two intervals during COVID-19 restrictions. The primary outcome was an assessment of sources of information and infant feeding practices in the context of COVID-19 restrictions. Data from 6934 responders (92.2% mothers) were analyzed. Most responders received information from multiple sources, with other parents, family members, or friends being the most frequently reported (48.6%), followed by webinars and experts’ recommendations (40.8%). COVID-19 restrictions largely did not impact the method of feeding, changes in feeding patterns, or complementary feeding introduction, although the latter was more likely to be impacted in families with average versus the best financial situations. Multivariate logistic regression analysis also most consistently showed that parents with a tertiary education and living in a city above 500 k were at higher odds of using webinars/experts’ recommendations, internet/apps, and professional expert guides and lower odds of claiming no need to deepen knowledge. This study clarifies major issues associated with complementary feeding practices during the implementation of COVID-19 restrictions in Poland.
Associations between Postprandial Gut Hormones and Markers of Bone Remodeling
Authors: Jensen Nina , Clemmensen Kim , Jensen Marie , Pedersen Hanne , Færch Kristine , Diaz Lars , Quist Jonas , Størling Joachim
Published: September 2021

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.
Milk Exosomes Transfer Oligosaccharides into Macrophages to Modulate Immunity and Attenuate Adherent-Invasive E. coli (AIEC) Infection
Authors: He Yingying , He Zhicheng , Leone Serena , Liu Shubai
Published: September 2021

Exosomes are abundance in human body fluids like urine, milk and blood. They act a critical role in extracellular and intracellular communication, intracellular trafficking and physiological regulation. Multiple immune-modulatory components, such as proteins, RNAs and carbohydrates (glycoproteins), have been found in human milk exosomes, which play immune-regulatory functions. However, little is known about oligosaccharides in milk exosomes, the “free sugars”, which act critical roles in the development of infant’s immature mucosal immune system. In this study, the profile of milk exosomes encapsulated human milk oligosaccharides (HMOs) was calibrated with characteristic oligosaccharides in colostrum and mature milk, respectively. The exosomes containing human milk oligosaccharides were uptaken by macrophages, which were responsible for the establishment of intestinal immunity. Furthermore, mice pretreated with exosome encapsulated HMOs were protected from AIEC infection and had significantly less LPS-induced inflammation and intestinal damage. Exosome encapsulated milk oligosaccharides are regarded to provide a natural manner for milk oligosaccharides to accomplish their critical functions in modifying newborn innate immunity. The understanding of the interaction between a mother’s breastfeeding and the development of an infant’s mucosal immune system would be advantageous. The transport of milk oligosaccharides to its target via exosome-like particles appears to be promising.
Core Strategies to Increase the Uptake and Use of Potassium-Enriched Low-Sodium Salt
Authors: Ajenikoko Adefunke , Ide Nicole , Shivashankar Roopa , Ge Zeng , Marklund Matti , Anderson Cheryl , Atun Amy , Thomson Alexander , Henry Megan , Cobb Laura
Published: September 2021

Excess sodium consumption and insufficient potassium intake contribute to high blood pressure and thus increase the risk of heart disease and stroke. In low-sodium salt, a portion of the sodium in salt (the amount varies, typically ranging from 10 to 50%) is replaced with minerals such as potassium chloride. Low-sodium salt may be an effective, scalable, and sustainable approach to reduce sodium and therefore reduce blood pressure and cardiovascular disease at the population level. Low-sodium salt programs have not been widely scaled up, although they have the potential to both reduce dietary sodium intake and increase dietary potassium intake. This article proposes a framework for a successful scale-up of low-sodium salt use in the home through four core strategies: availability, awareness and promotion, affordability, and advocacy. This framework identifies challenges and potential solutions within the core strategies to begin to understand the pathway to successful program implementation and evaluation of low-sodium salt use.
CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions
Authors: Nakagawa Yoshimi , Araki Masaya , Han Song-iee , Mizunoe Yuhei , Shimano Hitoshi
Published: September 2021

Cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor expressed in the liver and small intestine. The activity of CREBH is regulated not only at the transcriptional level but also at the posttranslational level. CREBH governs triglyceride metabolism in the liver by controlling gene expression, with effects including the oxidation of fatty acids, lipophagy, and the expression of apolipoproteins related to the lipoprotein lipase activation and suppression of lipogenesis. The activation and functions of CREBH are controlled in response to the circadian rhythm. On the other hand, intestinal CREBH downregulates the absorption of lipids from the diet. CREBH deficiency in mice leads to severe hypertriglyceridemia and fatty liver in the fasted state and while feeding a high-fat diet. Therefore, when crossing CREBH knockout (KO) mice with an atherosclerosis model, low-density lipoprotein receptor KO mice, these mice exhibit severe atherosclerosis. This phenotype is seen in both liver- and small intestine-specific CREBH KO mice, suggesting that CREBH controls lipid homeostasis in an enterohepatic interaction. This review highlights that CREBH has a crucial role in systemic lipid homeostasis to integrate cellular functions related to lipid metabolism.
Prevalence and Subtype Distribution of Blastocystis sp. in Diarrheic Pigs in Southern China
Authors: Wang Pei , Li Sen , Zou Yang , Hong Zhao-Wei , Wang Ping , Zhu Xing-Quan , Song De-Ping , Chen Xiao-Qing
Published: September 2021

Blastocystis sp. is a common pathogen that infects the intestines of humans and animals, causing a threat to public health. However, little information on the prevalence and subtypes of Blastocystis sp. in diarrheic pigs in China is available. Herein, 1254 fecal samples were collected from diarrheic pigs in 37 intensive pig farms in Hunan, Jiangxi, and Fujian provinces in southern China, and the prevalence and subtypes of Blastocystis sp. were investigated. Blastocystis sp. was detected by PCR assay, which amplified the small subunit rRNA (SSU rRNA) gene. Overall prevalence of Blastocystis sp. was 31.4% (394/1254), including 21.5% (66/307), 33.1% (99/299), 58.9% (56/95), and 31.3% (173/553) in suckling piglets, weaned piglets, fattening pigs, and sows, respectively. Moreover, age and region factors were significantly related to prevalence of Blastocystis sp. (p < 0.05). Four Blastocystis sp. subtypes were identified, including ST1, ST3, ST5, and ST14. The preponderant subtype was ST5 (76.9%, 303/394). To our knowledge, ST14 was firstly found in pigs in China. The human-pathogenic subtypes (ST1, ST3, ST5, and ST14) that were observed in this study indicate a potential threat to public health. These findings provided a new sight for studying the genetic structure of Blastocystis sp.
Medroxyprogesterone Acetate (MPA) Enhances HIV-1 Accumulation and Release in Primary Cervical Epithelial Cells by Inhibiting Lysosomal Activity
Authors: Jia Xiangxu , Shao Qiujia , Chaudhry Ahsen R. , Kinlock Ballington L. , Izban Michael G. , Zhang Hong-Ying , Villalta Fernando , Hildreth James E. K. , Liu Bindong
Published: September 2021

Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.
Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC
Authors: Ozbey Agustos Cetin , Combarel David , Poinsignon Vianney , Lovera Christine , Saada Esma , Mir Olivier , Paci Angelo
Published: September 2021

Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L−1. However, routine monitoring of trough plasma concentrations at fixed hours is difficult in daily practice. Herein, we aimed to characterize the pharmacokinetic (PK) profile of pazopanib and to identify a target area under the curve (AUC) more easily extrapolated from blood samples obtained at various timings after drug intake. A population pharmacokinetic (popPK) model was constructed to analyze pazopanib PK and to estimate the pazopanib clearance of a patient regardless of the time of sampling. Data from the therapeutic drug monitoring (TDM) of patients with cancer at Institute Gustave Roussy and a clinical study (phase I/II) that evaluates the tolerance to pazopanib were used. From the individual clearance, it is then possible to obtain the patient’s AUC. A target AUC for maximum efficacy and minimum side effects of 750 mg·h·L−1 was determined. The comparison of the estimated AUC with the target AUC would enable us to determine whether plasma exposure is adequate or whether it would be necessary to propose therapeutic adjustments.
State of the Art on Approved Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators and Triple-Combination Therapy
Authors: Meoli Aniello , Fainardi Valentina , Deolmi Michela , Chiopris Giulia , Marinelli Francesca , Caminiti Caterina , Esposito Susanna , Pisi Giovanna
Published: September 2021

Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations, affecting approximately 80,000 people worldwide. CF is a complex multi-organ monogenic autosomal recessive disorder caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the CFTR gene in 1989, more than 2000 mutations have been identified so far and about 240 can cause CF. Until recently, the treatment for CF was aimed to prevent and manage the manifestations of CFTR dysfunction, primarily recurrent pulmonary infections and pancreatic exocrine failure. Over the past few decades, the therapeutic approach to CF has been revolutionized by the development of a new class of small molecules called CFTR modulators that target specific defects caused by mutations in the CFTR gene. CFTR modulators have been shown to change profoundly the clinical course of the CF, leading to meaningful improvements in the lives of a large proportion of people of CF heterozygous for F508del, especially if started in young children. Further studies are needed to extend the use of triple CFTR modulation therapy also for young children in order to prevent the irreversible effects of the disease and for patients with very rare mutations with a personalized approach to treatment.
Contribution of CYP2D6 Functional Activity to Oxycodone Efficacy in Pain Management: Genetic Polymorphisms, Phenoconversion, and Tissue-Selective Metabolism
Authors: Deodhar Malavika , Turgeon Jacques , Michaud Veronique
Published: September 2021

Oxycodone is a widely used opioid for the management of chronic pain. Analgesic effects observed following the administration of oxycodone are mediated mostly by agonistic effects on the μ-opioid receptor. Wide inter-subject variability observed in oxycodone efficacy could be explained by polymorphisms in the gene coding for the μ-opioid receptor (OPRM1). In humans, oxycodone is converted into several metabolites, particularly into oxymorphone, an active metabolite with potent μ-opioid receptor agonist activity. The CYP2D6 enzyme is principally responsible for the conversion of oxycodone to oxymorphone. The CYP2D6 gene is highly polymorphic with encoded protein activities, ranging from non-functioning to high-functioning enzymes. Several pharmacogenetic studies have shown the importance of CYP2D6-mediated conversion of oxycodone to oxymorphone for analgesic efficacy. Pharmacogenetic testing could optimize oxycodone therapy and help achieve adequate pain control, avoiding harmful side effects. However, the most recent Clinical Pharmacogenetics Implementation Consortium guidelines fell short of recommending pharmacogenomic testing for oxycodone treatment. In this review, we (1) analyze pharmacogenomic and drug-interaction studies to delineate the association between CYP2D6 activity and oxycodone efficacy, (2) review evidence from CYP3A4 drug-interaction studies to untangle the nature of oxycodone metabolism and its efficacy, (3) report on the current knowledge linking the efficacy of oxycodone to OPRM1 variants, and (4) discuss the potential role of CYP2D6 brain expression on the local formation of oxymorphone. In conclusion, we opine that pharmacogenetic testing, especially for CYP2D6 with considerations of phenoconversion due to concomitant drug administration, should be appraised to improve oxycodone efficacy.
Preparation and In Vivo Evaluation of a Lidocaine Self-Nanoemulsifying Ointment with Glycerol Monostearate for Local Delivery
Authors: Kang Ji-Hyun , Yoo Kwang-Hwi , Park Hyo-Young , Hyun Seung-Min , Han Sang-Duk , Kim Dong-Wook , Park Chun-Woong
Published: September 2021

Lidocaine, a commonly used local anesthetic, has recently been developed into a number of ointment products to treat hemorrhoids. This study examined its efficient delivery to the dermis through the pharmaceutical improvement of hemorrhoid treatment ointments. We attempted to increase the amount of skin deposition of lidocaine by forming a nanoemulsion through the self-nanoemulsifying effect that occurs when glycerol monostearate (GMS) is saturated with water. Using Raman mapping, the depth of penetration of lidocaine was visualized and confirmed, and the local anesthetic effect was evaluated via an in vivo tail-flick test. Evaluation of the physicochemical properties confirmed that lidocaine was amorphous and evenly dispersed in the ointment. The in vitro dissolution test confirmed that the nanoemulsifying effect of GMS accelerated the release of the drug from the ointment. At a specific concentration of GMS, lidocaine penetrated deeper into the dermis; the in vitro permeation test showed similar results. When compared with reference product A in the tail-flick test, the L5 and L6 compounds containing GMS had a significantly higher anesthetic effect. Altogether, the self-nanoemulsifying effect of GMS accelerated the release of lidocaine from the ointment. The compound with 5% GMS, the lowest concentration that saturated the dermis, was deemed most appropriate.
Phytosomes as an Emerging Nanotechnology Platform for the Topical Delivery of Bioactive Phytochemicals
Authors: Alharbi Waleed S. , Almughem Fahad A. , Almehmady Alshaimaa M. , Jarallah Somayah J. , Alsharif Wijdan K. , Alzahrani Nouf M. , Alshehri Abdullah A.
Published: September 2021

The emergence of phytosome nanotechnology has a potential impact in the field of drug delivery and could revolutionize the current state of topical bioactive phytochemicals delivery. The main challenge facing the translation of the therapeutic activity of phytochemicals to a clinical setting is the extremely low absorption rate and poor penetration across biological barriers (i.e., the skin). Phytosomes as lipid-based nanocarriers play a crucial function in the enhancement of pharmacokinetic and pharmacodynamic properties of herbal-originated polyphenolic compounds, and make this nanotechnology a promising tool for the development of new topical formulations. The implementation of this nanosized delivery system could enhance the penetration of phytochemicals across biological barriers due to their unique physiochemical characteristics, improving their bioavailability. In this review, we provide an outlook on the current knowledge of the biological barriers of phytoconstituents topical applications. The great potential of the emerging nanotechnology in the delivery of bioactive phytochemicals is reviewed, with particular focus on phytosomes as an innovative lipid-based nanocarrier. Additionally, we compared phytosomes with liposomes as the gold standard of lipid-based nanocarriers for the topical delivery of phytochemicals. Finally, the advantages of phytosomes in topical applications are discussed.
Improvement of Imiquimod Solubilization and Skin Retention via TPGS Micelles: Exploiting the Co-Solubilizing Effect of Oleic Acid
Authors: Ghezzi Martina , Pescina Silvia , Delledonne Andrea , Ferraboschi Ilaria , Sissa Cristina , Terenziani Francesca , Remiro Paula De Freitas Rosa , Santi Patrizia , Nicoli Sara
Published: September 2021

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier. The formulations were characterized in terms of particle size, zeta potential and stability over time and micelles performance on the skin was evaluated through the quantification of imiquimod retention in the skin layers and the visualization of a micelle-loaded fluorescent dye by two-photon microscopy. The results showed that imiquimod solubility strictly depends on the nature and concentration of the co-encapsulated compounds. The micellar formulation based on TPGS and oleic acid was identified as the most interesting in terms of both drug solubility (which was increased from few µg/mL to 1154.01 ± 112.78 µg/mL) and micellar stability (which was evaluated up to 6 months from micelles preparation). The delivery efficiency after the application of this formulation alone or incorporated in hydrogels showed to be 42- and 25-folds higher than the one of the commercial creams.
Targeting BRAF Activation as Acquired Resistance Mechanism to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small-Cell Lung Cancer
Authors: Aboubakar Nana Frank , Ocak Sebahat
Published: September 2021

Osimertinib has become a standard of care in the first-line treatment of advanced-stage non-small-cell lung cancer (NSCLC) harboring exon 19 and 21 activating mutations in the EGFR gene. Nevertheless, the 18.9-month median progression-free survival emphasizes the fact that resistance to osimertinib therapy is inevitable. Acquired resistance mechanisms to osimertinib in EGFR-driven NSCLC include MET amplification, EGFR C797S mutation, neuroendocrine differentiation, small-cell lung carcinoma histologic transformation, PD-L1 and KRAS amplifications and ESR1-AKAP12 and MKRN1-BRAF translocations, as well as BRAF V600 mutation. This last one represents 3% of the acquired resistance mechanisms to osimertinib. In this review, we discuss the rationale for EGFR/BRAF/MEK co-inhibition in the light of a clinical case of EGFR-mutant NSCLC developing a BRAF V600 mutation as an acquired resistance mechanism to osimertinib and responding to the association of osimertinib plus dabrafenib and trametinib. Additionally, we discuss the acquired resistance mechanisms to osimertinib plus dabrafenib and trametinib combination in that context.
Laser Fluorescence and Extinction Methods for Measuring the Flow and Composition of Milk in a Milking Machine
Authors: Kirsanov Vladimir V. , Shkirin Alexey V. , Pavkin Dmitriy Yu. , Ignatenko Dmitry N. , Danielyan Georgy L. , Khakimov Artyom R. , Bunkin Nikolai F.
Published: September 2021

Automation of milking systems is linked to accurate measurement of fluctuations in milk flow during milking. To assess the fluctuations of the milk flow, the formation and movement of milk portions in the milking machine-milk pipeline system was studied. By considering the movement of a milk plug along the milk pipeline, a hydraulic model of the formation of a critical volume of milk in the milking machine manifold was compiled. In practice, the most expedient way of determining milk flow parameters may be to measure the laser fluorescent and extinction responses of moving air-milk mixture. We have implemented a new laser sensing method for measuring the flow rate and composition of milk on the basis of counting the optical response pulses received from moving dispersed components by a CCD array or a randomized fiber optic bundle. Using the developed laser sensors, the theoretical model of milk flow was tested.
Application of Visible Aquaphotomics for the Evaluation of Dissolved Chemical Concentrations in Aqueous Solutions
Authors: Bozhynov Vladyslav , Kovacs Zoltan , Cisar Petr , Urban Jan
Published: September 2021

This paper introduces novel research in aquaphotomics, extending the study of water–light interactions to the visible spectral range. This approach can potentially reduce the cost and increase the speed of spectral measurements, while providing additional information by extending the useful range in spectrophotometry. To demonstrate our method, we investigated the applicability of the visible spectral range for the quantification of NaCl dissolved in aqueous samples. Spectral measurements were conducted using a visible spectrometer in the range of 380–730 nm. The evaluation of molecular species concentration was based on multivariate analysis (MVA). Principal component analysis (PCA) showed a separation of all groups of samples by salt concentration. The partial least squares regression (PLSR) model presented high accuracy and a relationship between spectral variables in the visible range and NaCl concentration in water. The validity of the regression model was confirmed through independent prediction of NaCl concentration values in test samples with unknown concentrations. The presented results demonstrate the success of the approach in evaluating concentration changes in visible light, and thus extend the measurable spectral range of such analysis.
Phycology: Algae for Food, Feed, Fuel and the Planet
Authors: Schenk Peer M.
Published: September 2021

I often like to tell my students: “It does not matter what the question is, “algae” is the answer [...]
Local Regions with Expanding Extra Dimensions
Authors: Bronnikov Kirill A. , Rubin Sergey G.
Published: September 2021

In this paper possible spatial domains, containing expanding extra dimensions, are studied. It is demonstrated that these domains are predicted in the framework of f(R) gravity (where R is the scalar curviture) and could appear due to quantum fluctuations during inflation. The interior of the domains is shown to be characterized by the multidimensional curvature ultimately tending to zero and a slowly growing size of the extra dimensions.
Fucoid Macroalgae Have Distinct Physiological Mechanisms to Face Emersion and Submersion Periods in Their Southern Limit of Distribution
Authors: Martins Maria , Soares Cristiano , Figueiredo Inês , Sousa Bruno , Torres Ana Catarina , Sousa-Pinto Isabel , Veiga Puri , Rubal Marcos , Fidalgo Fernanda
Published: September 2021

During high tide, macroalgae are submersed, facing adequate environmental conditions, however, at low tide, these species can be exposed to high UV radiation and desiccation, leading to an overproduction of reactive oxygen species, causing oxidative stress. Since intertidal organisms present differential sensitivity to abiotic fluctuations, this study aimed to evaluate the physiological responses [photosynthetic pigments, hydrogen peroxide (H2O2), lipid peroxidation (LP), and thiols and proline] of three macroalgae, from different intertidal levels, towards tidal regimes. Samples of Pelvetia canaliculata, Ascophyllum nodosum, and Fucus serratus were collected from beaches located on the southern limit of distribution in periods of potential stress (Summer and Spring), under low and high tide. The photosynthetic pigments of P. canaliculata and F. serratus were generally higher during low tide, and the oxidative damage evidenced by H2O2 and LP increased in the Summer, while A. nodosum showed greater oxidative damage in the Spring. While thiol content did not change, proline levels were species- and tidal-specific among sampling dates. P. canaliculata presented higher resilience to unfavorable conditions, while F. serratus was the most sensitive species. The physiological responses analyzed were species-specific, pointing to the high susceptibility of low intertidal organisms to expected extreme climatic events.