bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiographic Bone Loss and Its Relation to Patient-Specific Risk Factors, LDL Cholesterol, and Vitamin D: A Cross-Sectional Study
Authors: Thim Teresa , Scholz Konstantin Johannes , Hiller Karl-Anton , Buchalla Wolfgang , Kirschneck Christian , Fleiner Jonathan , Woelber Johan Peter , Cieplik Fabian
Published: February 2022

The influence of patient-specific factors such as medical conditions, low-density lipoprotein cholesterol (LDL-C) or levels of 25-hydroxyvitamin D (25OHD) on periodontal diseases is frequently discussed in the literature. Therefore, the aim of this retrospective cross-sectional study was to evaluate potential associations between radiographic bone loss (RBL) and patient-specific risk factors, particularly LDL-C and 25OHD levels. Patients from a dental practice, who received full-mouth cone beam CTs (CBCTs) and blood-sampling in the course of implant treatment planning, were included in this study. RBL was determined at six sites per tooth from CBCT data. LDL-C and 25OHD levels were measured from venous blood samples. Other patient-specific risk factors were assessed based on anamnesis and dental charts. Statistical analysis was performed applying non-parametric procedures (Mann–Whitney U tests, error rates method). Data from 163 patients could be included in the analysis. RBL was significantly higher in male patients, older age groups, smokers, patients with high DMFT (decayed/missing/filled teeth) score, lower number of teeth, and high LDL-C levels (≥160 mg/dL). Furthermore, patients with high 25OHD levels (≥40 ng/mL) exhibited significantly less RBL. In summary, RBL was found to be associated with known patient-specific markers, particularly with age and high LDL-C levels.
Anti-Obesity Effects of Polymethoxyflavone-Rich Fraction from Jinkyool (Citrus sunki Hort. ex Tanaka) Leaf on Obese Mice Induced by High-Fat Diet
Authors: Jin Yeong-Jun , Jang Mi-Gyeong , Kim Jae-Won , Baek Songyee , Ko Hee-Chul , Hur Sung-Pyo , Kim Se-Jae
Published: February 2022

Polymethoxyflavones (PMFs) are flavonoids exclusively found in certain citrus fruits and have been reported to be beneficial to human health. Most studies have been conducted with PMFs isolated from citrus peels, while there is no study on PMFs isolated from leaves. In this study, we prepared a PMF-rich fraction (PRF) from the leaves of Citrus sunki Hort ex. Tanaka (Jinkyool) and investigated whether the PRF could improve metabolic decline in obese mice induced by a high-fat diet (HFD) for 5 weeks. The HFD-induced obese mice were assigned into HFD, OR (HFD + orlistat at 15.6 mg/kg of body weight/day), and PRF (HFD + 50, 100, and 200 mg/kg of body weight/day) groups. Orlistat and PRF were orally administered for 5 weeks. At the end of the experiment, the serum biochemical parameters, histology, and gene expression profiles in the tissues of each group were analyzed. The body weight gain of the obese mice was significantly reduced after orlistat and PRF administration for 5 weeks. PRF effectively improved HFD-induced insulin resistance and dyslipidemia. Histological analysis in the liver demonstrated that PRF decreased adipocyte size and potentially improved the liver function, as it inhibited the incidence of fatty liver. PRF activated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and hormone-sensitive lipase (HSL) in HFD-induced obese mice. Moreover, liver transcriptome analysis revealed that PRF administration enriched genes mainly related to fatty-acid metabolism and immune responses. Overall, these results suggest that the PRF exerted an anti-obesity effect via the modulation of lipid metabolism.
Associations of Metabolic and Obstetric Risk Parameters with Timing of Lactogenesis II
Authors: Mullen Amber J. , O’Connor Deborah L. , Hanley Anthony J. , Piedimonte Giovanni , Wallace Maeve , Ley Sylvia H.
Published: February 2022

Lactogenesis II is the onset of copious milk production following parturition. Delayed onset of lactogenesis II (DLII) often contributes to poorer lactation performance, which may adversely affect maternal and child health. The present study aims to identify the metabolic and obstetric risk factors for DLII in a secondary analysis of a prospective cohort study following pregnant women through postpartum. We defined the onset of lactogenesis II as delayed if it occurred ≥72 h postpartum. Multiple logistic regression analyses were conducted to evaluate the associations of metabolic and obstetric variables with DLII. Median onset of lactogenesis II was 72.4 h (IQR 60.4–91.6) postpartum, and 55.4% (98 of 177) of women experienced DLII. Time to first breast contact ≥ 2 h postpartum compared to ≤1 h postpartum was associated with DLII (OR 2.71 95% CI 1.12–6.53) with adjustment for age, race, pregravid BMI, primiparity, and mode of delivery, while metabolic variables were not significantly associated with DLII. In this comprehensive examination of potential metabolic and obstetric parameters, earlier timing of putting the infant to the breast remained significantly associated with earlier onset of milk coming in after consideration of the other potential risk factors. Obstetrical practices, including putting the baby to the breast later, may have an important impact on the timing of lactation, and interventions are needed to address this concern.
Interaction of Protein Preloads and Physical Activity on Intake of an Ultra-Processed, High Sugar/High Fat Food/Low Protein Food
Authors: Nasser Jennifer A. , Albajri Eram , Lanza Lisa , Gilman Abigail , Altayyar Mansour , Thomopoulos Dimitra , Bruneau Michael
Published: February 2022

“Loss of control, LOC” eating is a major contributor to the development of obesity. Dietary protein is known to promote satiety, but little attention has been paid to the ability of protein, consumed in close proximity to snacking (20 min), to reduce the intake of ultra-processed, low-protein snack foods. We hypothesized that a high-protein preload (HP, 8 g of protein) consumed in close proximity to eating an ultra-processed snack food would reduce intake of the snack food as compared to a low-protein preload (LP, 1.2 g of protein). Two laboratory test meals were conducted, and the intake of ice cream (1.99 kcal/gram) after consuming dairy-based liquid preloads was measured. Habitual physical activity, a potential modulator of satiety, was assessed by a self-reporting questionnaire. Thirty (responders) out of 50 participants reduced their intake of ice cream after the HP preload, with a significant difference in intake observed between the responders and non-responders (−30 ± 25 and 18 ± 18 g, F (1, 49) = 54.36, p < 0.001 for responders and non-responders, respectively). Our data demonstrate that protein consumed in close proximity to ultra-processed snack food can reduce caloric intake by ~60 kcal, which could potentially reduce body weight by at least 5 pounds per year.
Nutrition and Diet in Rheumatoid Arthritis
Authors: Cutolo Maurizio , Nikiphorou Elena
Published: February 2022

Rheumatic and musculoskeletal diseases (RMDs) are chronic systemic immune/inflammatory conditions characterized by the interaction between gene predisposition, autoimmunity and environmental factors [...]
The Association between Online Learning and Food Consumption and Lifestyle Behaviors and Quality of Life in Terms of Mental Health of Undergraduate Students during COVID-19 Restrictions
Authors: Chusak Charoonsri , Tangmongkhonsuk Mutthatinee , Sudjapokinon Jutaporn , Adisakwattana Sirichai
Published: February 2022

The COVID-19 pandemic caused the abrupt replacement of traditional face-to-face classes into online classes. Several studies showed that online teaching and learning produced adverse mental health for students. However, no research has been conducted so far analyzing the association between the duration of online and food consumption and lifestyle behaviors and quality of life in terms of mental health of undergraduate students. This study aimed to determine the association between the duration of online learning and food consumption behaviors, lifestyles, and quality of life in terms of mental health among Thai undergraduate students during COVID-19 restrictions. A cross-sectional online survey of 464 undergraduate students was conducted at Chulalongkorn University, Bangkok, Thailand, between March and May 2021. The majority of undergraduate students stated that they spent 3–6 h per day on online learning (76.1%) and used their digital devices such as computers, tablets, or smartphones more than 6 h per day (76.9%). In addition, they had 75.4% of skipping breakfast (≥3 times/week) and 63.8% of sleep duration (6–8 h/day). A higher proportion of students who drank tea or coffee with milk and sugar while online learning was observed. The results found that the increased duration of online learning was significantly associated with skipping breakfast and the frequency of sugary beverage consumption. On the other hand, the increased computer, tablet, and smartphone usage for online learning was correlated with lower sleep duration and a poor quality of life in terms of mental health. The findings from this study contribute to a report of the association between online learning and food consumption and lifestyle behaviors and quality of life of undergraduate students, emphasizing the necessity for intervention strategies to promote healthy behaviors.
An Experimental Evaluation of Toxicity Effects of Sodium Chloride on Oviposition, Hatching and Larval Development of Aedes albopictus
Authors: Guo Xiang , Zhou Siyun , Wu Jing , Zhang Xiaoqing , Wang Yuji , Li Zixuan , Chen Xiao-Guang , Zhou Xiaohong
Published: February 2022

Dengue virus, one of the most important mosquito-borne viruses, has shown a sharp upward trend, spreading around the world in recent years. Control of vectors Aedes aegypti and Ae. albopictus remains crucial for blocking dengue transmission. The lethal ovitrap (LO) is one of the cost-effective traps based on the classic “lure and kill” strategy, and finding a proper long-lasting effective toxin is key to achieving the desired effect. The concentration of inorganic salts of habitat environment plays a strong role in affecting oviposition, hatching, and development of mosquitoes, but the potential insecticide activity of Sodium Chloride (NaCl) in habitat water as well as LO still lacks research. In this study, we carried out laboratory experiments to systematically explore the effects of different concentrations of NaCl solutions on oviposition, egg hatching, and larval development of Ae. albopictus. Consequently, Ae. albopictus was found to prefer freshwater to lay eggs; whereas 48.8 ± 2.6% eggs were laid in freshwater and 20% in ≥1.0% brackish water, few eggs were laid in 3.0% NaCl solution. Compared with egg hatching, larval development of Ae. albopictus presented a higher sensibility to NaCl concentration. The mortality of the 3rd–4th larvae in 1.0% NaCl solution was 83.8 ± 8.7%, while in 3.0% it reached 100%. Considering the cumulative effect of NaCl, when NaCl concentration was ≥1.0%, no eggs could successfully develop into adults. These data suggested that NaCl solutions with a concentration ≥1.0% can be used as an effective cheap insecticide for Ae. albopictus in subtropical inland aquatic habitats, and also as the “kill” toxin in LOs. Meanwhile, the concentration range from 0 to 2.0% of NaCl solution has the potential to be used as the “lure” in LOs. The technological processes of how to use NaCl as insecticide or in LOs still needs further in-depth exploration.
Call for Caution to Consider Babesia bovis and Babesia bigemina as Anthropozoonotic Agents in Colombia. Comment on Kumar et al. The Global Emergence of Human Babesiosis. Pathogens 2021, 10, 1447
Authors: Silva-Ramos Carlos Ramiro , Faccini-Martínez Álvaro A.
Published: February 2022

Currently, six species and two genetic variants within Babesia genus have been confirmed as human pathogens. Babesia bovis and Babesia bigemina are causative agents of bovine babesiosis, and, in spite of the worldwide distribution of those species and their vectors, no description of related human cases has been reported. As a contribution, we would like to address the articles which claim the alleged role of B. bovis and B. bigemina as anthropozoonotic pathogens in Colombia.
Rabies Virus Variants Detected from Cougar (Puma concolor) in Mexico 2000–2021
Authors: Garcés-Ayala Fabiola , Aguilar-Setién Álvaro , Almazán-Marín Cenia , Cuautle-Zavala Claudia , Chávez-López Susana , Martínez-Solís David , Gómez-Sierra Mauricio , Sandoval-Borja Albert , Escamilla-Ríos Beatriz , López-Martínez Irma , Aréchiga-Ceballos Nidia
Published: February 2022

In 2019, the World Health Organization (WHO) and the Pan-American Health Organization (PAHO) recognized Mexico as a country free of human rabies transmitted by dogs. Nevertheless, the sylvatic cycle remains as a public health concern in the country. Although cougars (Puma concolor) are not reservoirs of any rabies virus variant (RVV), these felines could act as vectors at the top of the food chain, and their relationships with other organisms must be considered important for the regulatory effect on their prey’s populations. In this study, genetic and antigenic characterization was performed on all cougar rabies cases diagnosed at the Rabies Laboratory Network of the Ministry of Health (RLNMH) in Mexico from 2000 to 2021. Samples from other species, a skunk, a horse (Equus caballus) (attacked by a cougar), and a gray fox (Urocyon cineroargenteus), were included as reference. Rabies cases in cougars were restricted to two Northern states of Mexico (Sonora and Chihuahua). Five out of six samples of cougars were RVV7 (Arizona gray fox RVV) and one from Sonora was RVV1. Interestingly, there is no evidence of RVV1 in dogs in the Northern states since the 1990s but skunk species now harbor this RVV1 in this region of the country.
Plant- and Bacteria-Derived Compounds with Anti-Philasterides dicentrarchi Activity
Authors: Sueiro Rosa Ana , Leiro José Manuel , Blanco-Abad Verónica , Raaijmakers Jos , de Bruijn Irene , Dirks Ron P. H. , Lamas Jesús
Published: February 2022

Philasterides dicentrarchi is a scuticociliate that causes high mortalities in farmed fish. Although vaccination is an effective method to prevent scuticociliatosis caused by the homologous serotype, a universal vaccine has not been developed yet. Many compounds have been shown to be toxic to this ciliate species; moreover, most of them are toxic to aquatic life and cannot be used to prevent the disease. We have evaluated the toxicity to P. dicentrarchi of several compounds of natural origin to be used to reduce parasite levels in the seawater. Ciliates were exposed to several compound concentrations, and the mortality was determined at several incubation times. Tomatine, plumbagin and 2′,4′-dihydroxychalcone displayed the highest anticiliate activity, with a dose-dependent response. The effects of these compounds on the EPC cell line were also evaluated, finding that 2′,4′-dihydroxychalcone displayed the lowest toxicity to fish cells. At 7.54 μM, 2′,4′-dihydroxychalcone inhibited 50% parasite growth but only killed about 10% of EPC cells after 24 h incubation. Finally, we evaluated the toxicity of Pseudomonas H6 surfactant (PS) to P. dicentrarchi, finding that PS was toxic to the ciliate but showed lower toxicity to EPC cells. At a concentration of 7.8 μg/mL (LC50 for the ciliate after 3 h incubation), PS killed 14.9% of EPC cells. We conclude that 2′,4′-dihydroxychalcone, and PS could be used to reduce parasite levels in seawater, thus decreasing the risk of scuticociliatosis infection in cultured fish.
Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms
Authors: Han Qing , Zheng Bang , Daines Luke , Sheikh Aziz
Published: February 2022

Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18–39), dyspnoea (18%, 95% CI: 13–24), arthromyalgia (26%, 95% CI: 8–44), depression (23%, 95% CI: 12–34), anxiety (22%, 95% CI: 15–29), memory loss (19%, 95% CI: 7–31), concentration difficulties (18%, 95% CI: 2–35), and insomnia (12%, 95% CI: 7–17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients.
Patients with Obesity and a History of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study
Authors: Cummings Tammy H. , Magagnoli Joseph , Hardin James W. , Sutton S. Scott
Published: February 2022

Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database. Methods: The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of influenza with a diagnosis of fever, cough, influenza, or acute upper respiratory infection in an outpatient setting. The study outcome was death after diagnosis of influenza. Cohorts were formed using diabetes status and metformin exposure prior to a positive influenza diagnosis. Hazard ratios for mortality were estimated using a cox proportional hazards model adjusting for baseline covariates and a sub-analysis was conducted utilizing propensity score matching. A greedy nearest neighbor algorithm was utilized to match 1 to 1 non-metformin diabetic controls and non-diabetic controls to diabetic patients receiving metformin. Results: A total of 3551 patients met the inclusion criteria and were evaluated in our study. The cohorts consisted of 1461 patients in the non-diabetic cohort, 1597 patients in the diabetic / metformin cohort, and 493 patients in the diabetic no metformin cohort. Compared to non-diabetic patients, diabetic patients with metformin had a lower rate of death (aHR 0.78, 95% CI 0.609–0.999). There was not a statistical difference between the non-diabetic patients and the diabetic patients without metformin (aHR 1.046, 95% CI 0.781–1.400). The propensity score matched cohorts revealed consistent results with the primary analysis. Conclusion: Our results demonstrated patients with obesity and a history of metformin treatment have lower influenza mortality.
Methods of Inactivation of Highly Pathogenic Viruses for Molecular, Serology or Vaccine Development Purposes
Authors: Elveborg Simon , Monteil Vanessa , Mirazimi Ali
Published: February 2022

The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic viruses are represented by enveloped RNA viruses belonging to the Togaviridae, Flaviviridae, Filoviridae, Arenaviridae, Hantaviridae, Peribunyaviridae, Phenuiviridae, Nairoviridae and Orthomyxoviridae families. Here, we summarize inactivation methods for these virus families that allow for subsequent molecular and serological analysis or vaccine development. The techniques identified here include: treatment with guanidium-based chaotropic salts, heat inactivation, photoactive compounds such as psoralens or 1.5-iodonaphtyl azide, detergents, fixing with aldehydes, UV-radiation, gamma irradiation, aromatic disulfides, beta-propiolacton and hydrogen peroxide. The combination of simple techniques such as heat or UV-radiation and detergents such as Tween-20, Triton X-100 or Sodium dodecyl sulfate are often sufficient for virus inactivation, but the efficiency may be affected by influencing factors including quantity of infectious particles, matrix constitution, pH, salt- and protein content. Residual infectivity of the inactivated virus could have disastrous consequences for both laboratory/healthcare personnel and patients. Therefore, the development of inactivation protocols requires careful considerations which we review here.
Determination of Phloridzin and Other Phenolic Compounds in Apple Tree Leaves, Bark, and Buds Using Liquid Chromatography with Multilayered Column Technology and Evaluation of the Total Antioxidant Activity
Authors: Adamcová Anežka , Horna Aleš , Šatínský Dalibor
Published: February 2022

Apples are known to be a rich source of phenolic compounds, however detailed studies about their content in the individual parts of apple trees are reported rarely. For this purpose, we tested various stationary phases for the determination of phenolic compounds in leaves, bark, and buds. Phloridzin, phloretin, chlorogenic acid, rutin, and quercitrin were analyzed with high performance liquid chromatography coupled with diode array detection. A YMC Triart C18-ExRS 150 × 4.6 mm, 5 µm particle size analytical column with multilayered particle technology was used. The separation was performed with a mobile phase that consisted of acetonitrile and 0.1% phosphoric acid, according to the gradient program, at a flow rate of 1 mL/min for 12.50 min. The concentration of phenolic compounds from 13 cultivars was in the range of 64.89–106.01 mg/g of dry weight (DW) in leaves, 70.81–113.18 mg/g DW in bark, and 100.68–139.61 mg/g DW in buds. Phloridzin was a major compound. The total antioxidant activity was measured using flow analysis and the correlation with the total amount of phenolic compounds was found. This finding can lead to the re-use of apple tree material to isolate substances that can be utilized in the food, pharmaceutical, or cosmetics industries.
From the North Sea to Drug Repurposing, the Antiseizure Activity of Halimide and Plinabulin
Authors: Copmans Daniëlle , Kildgaard Sara , Roux Emma , Partoens Michèle , Steurs Gert , Wang Xinhui , De Borggraeve Wim M. , Esguerra Camila V. , Crawford Alexander D. , Larsen Thomas O. , de Witte Peter A. M.
Published: February 2022

PharmaSea performed large-scale in vivo screening of marine natural product (MNP) extracts, using zebrafish embryos and larvae, to identify compounds with the potential to treat epilepsy. In this study, we report the discovery of two new antiseizure compounds, the 2,5-diketopiperazine halimide and its semi-synthetic analogue, plinabulin. Interestingly, these are both known microtubule destabilizing agents, and plinabulin could have the potential for drug repurposing, as it is already in clinical trials for the prevention of chemotherapy-induced neutropenia and treatment of non-small cell lung cancer. Both halimide and plinabulin were found to have antiseizure activity in the larval zebrafish pentylenetetrazole (PTZ) seizure model via automated locomotor analysis and non-invasive local field potential recordings. The efficacy of plinabulin was further characterized in animal models of drug-resistant seizures, i.e., the larval zebrafish ethyl ketopentenoate (EKP) seizure model and the mouse 6 Hz psychomotor seizure model. Plinabulin was observed to be highly effective against EKP-induced seizures, on the behavioral and electrophysiological level, and showed activity in the mouse model. These data suggest that plinabulin could be of interest for the treatment of drug-resistant seizures. Finally, the investigation of two functional analogues, colchicine and indibulin, which were observed to be inactive against EKP-induced seizures, suggests that microtubule depolymerization does not underpin plinabulin’s antiseizure action.
Design, Synthesis, and Biological Evaluation of 4,4’-Difluorobenzhydrol Carbamates as Selective M1 Antagonists
Authors: Kilian Jonas , Ozenil Marius , Millard Marlon , Fürtös Dorka , Maisetschläger Verena , Holzer Wolfgang , Wadsak Wolfgang , Hacker Marcus , Langer Thierry , Pichler Verena
Published: February 2022

Due to their important role in mediating a broad range of physiological functions, muscarinic acetylcholine receptors (mAChRs) have been a promising target for therapeutic and diagnostic applications alike; however, the list of truly subtype-selective ligands is scarce. Within this work, we have identified a series of twelve 4,4’-difluorobenzhydrol carbamates through a rigorous docking campaign leveraging commercially available amine databases. After synthesis, these compounds have been evaluated for their physico–chemical property profiles, including characteristics such as HPLC-logD, tPSA, logBB, and logPS. For all the synthesized carbamates, these characteristics indicate the potential for BBB permeation. In competitive radioligand binding experiments using Chinese hamster ovary cell membranes expressing the individual human mAChR subtype hM1-hM5, the most promising compound 2 displayed a high binding affinitiy towards hM1R (1.2 nM) while exhibiting modest-to-excellent selectivity versus the hM2-5R (4–189-fold). All 12 compounds were shown to act in an antagonistic fashion towards hM1R using a dose-dependent calcium mobilization assay. The structural eligibility for radiolabeling and their pharmacological and physico–chemical property profiles render compounds 2, 5, and 7 promising candidates for future position emission tomography (PET) tracer development.
In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
Authors: Kovar Lukas , Wien Lena , Selzer Dominik , Kohl Yvonne , Bals Robert , Lehr Thorsten
Published: February 2022

Static in vitro permeation experiments are commonly used to gain insights into the permeation properties of drug substances but exhibit limitations due to missing physiologic cell stimuli. Thus, fluidic systems integrating stimuli, such as physicochemical fluxes, have been developed. However, as fluidic in vitro studies display higher complexity compared to static systems, analysis of experimental readouts is challenging. Here, the integration of in silico tools holds the potential to evaluate fluidic experiments and to investigate specific simulation scenarios. This study aimed to develop in silico models that describe and predict the permeation and disposition of two model substances in a static and fluidic in vitro system. For this, in vitro permeation studies with a 16HBE cellular barrier under both static and fluidic conditions were performed over 72 h. In silico models were implemented and employed to describe and predict concentration–time profiles of caffeine and diclofenac in various experimental setups. For both substances, in silico modeling identified reduced apparent permeabilities in the fluidic compared to the static cellular setting. The developed in vitro–in silico modeling framework can be expanded further, integrating additional cell tissues in the fluidic system, and can be employed in future studies to model pharmacokinetic and pharmacodynamic drug behavior.
The Potential Application of Extracellular Vesicles from Liquid Biopsies for Determination of Pharmacogene Expression
Authors: Habtemariam Henok D. , Guchelaar Henk-Jan
Published: February 2022

Pharmacogenomics (PGx) entails the study of heritability of drug response. This may include both variability in genes related to pharmacokinetics (drug absorption, distribution, metabolism and excretion) and pharmacodynamics (e.g., drug receptors or signaling pathways). Individualizing drug therapy taking into account the genetic profile of the patient has the potential to make drug therapy safer and more effective. Currently, this approach relies on the determination of genetic variants in pharmacogenes by genotyping. However, it is widely acknowledged that large variability in gene expression is attributed to non-structural genetic variants. Therefore, at least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting. Extracellular vesicles (EVs) are lipid encapsulated structures that contain cargo such as lipids, nucleic acids and proteins. Since their cargo is tissue- and cell-specific they can be used to determine the expression of pharmacogenes in the liver. In this review, we describe methods of EV isolation and the potential of EVs isolated from liquid biopsies as a tool to determine the expression of pharmacogenes for use in personalized medicine.
Ethanolic Fenugreek Extract: Its Molecular Mechanisms against Skin Aging and the Enhanced Functions by Nanoencapsulation
Authors: Eaknai Waleewan , Bunwatcharaphansakun Phichaporn , Phungbun Chutikorn , Jantimaporn Angkana , Chaisri Sasikan , Boonrungsiman Suwimon , Nimmannit Ubonthip , Khongkow Mattaka
Published: February 2022

Fenugreek, or Trigonella foenum-graecum L. (family Leguminosae) seeds, are typically used as food supplements to increase postnatal lactation. Fenugreek extract displays antioxidative and anti-inflammatory properties, but its mechanisms against skin aging have not been exploited. In this research, we are the first to define an in vitro collagenase inhibitory activity of fenugreek extract (IC50 = 0.57 ± 0.02 mg/mL), which is 2.6 times more potent than vitamin C (IC50 = 1.46 mg/mL). Nanoencapsulation has been applied to improve the extract stability, and subsequently enhanced its bioactivities. Liponiosome encapsulating fenugreek extract (LNF) was prepared using a high-speed homogenizer, resulting in homogeneous spherical nanoparticles with sizes in the range of 174.7 ± 49.2 nm, 0.26 ± 0.04 in PdI, and 46.6 ± 7.4% of entrapment efficiency. LNF formulation significantly facilitated a sustained release and significantly enhanced skin penetration over the extracts, suggesting a potential use of LNF for transdermal delivery. The formulated LNF was highly stable, not toxic to human fibroblast, and was able to enhance cell viability, collagen production, and inhibit MMP1, MMP9, IL-6, and IL-8 secretions compared to the extract in the co-cultured skin model. Therefore, ethanolic fenugreek extract and its developed LNF display molecular mechanisms against skin aging and could potentially be used as an innovative ingredient for the prevention of skin aging.
Limited Impact of the Protein Corona on the Cellular Uptake of PEGylated Zein Micelles by Melanoma Cancer Cells
Authors: Meewan Jitkasem , Somani Sukrut , Laskar Partha , Irving Craig , Mullin Margaret , Woods Stuart , Roberts Craig W. , Alzahrani Abdullah R. , Ferro Valerie A. , McGill Suzanne , Weidt Stefan , Burchmore Richard , Dufès Christine
Published: February 2022

The formation of a protein layer “corona” on the nanoparticle surface upon entry into a biological environment was shown to strongly influence the interactions with cells, especially affecting the uptake of nanomedicines. In this work, we present the impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. Zein was successfully conjugated with poly(ethylene glycol) (PEG) of varying chain lengths (5K and 10K) and assembled into micelles. Our results demonstrate that PEGylation conferred stealth effects to the zein micelles. The presence of human plasma did not impact the uptake levels of the micelles by melanoma cancer cells, regardless of the PEG chain length used. In contrast, it decreased the uptake by macrophages and dendritic cells. These results therefore make PEGylated zein micelles promising as potential drug delivery systems for cancer therapy.
Prevalence and Risk Factors of Augmented Renal Clearance: A Systematic Review and Meta-Analysis
Authors: Hefny Fatma , Stuart Anna , Kung Janice Y. , Mahmoud Sherif Hanafy
Published: February 2022

Kidney function assessment in the critically ill overlooks the possibility for hyperfunctioning kidneys, known as augmented renal clearance (ARC), which could contribute to therapeutic failures in the intensive care unit (ICU). The aim of this research is to conduct a systematic review and meta-analysis of prevalence and risk factors of ARC in the critically ill. MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations and Theses Global databases were searched on 27 October 2020. We included studies conducted in critically ill adults who reported the prevalence and/or risk factors of ARC. We evaluated study quality using the Joanna Briggs Institute appraisal tool. Case reports, reviews, editorials and commentaries were excluded. We generated a random-effects meta-analytic model using the inverse variance method and visualized the pooled estimates using forest plots. Seventy studies were included. The pooled prevalence (95% CI) was 39% (34.9–43.3). Prevalence for neuro, trauma, mixed and sepsis ICUs were 74 (55–87), 58 (48–67), 36 (31–41) and 33 (21–48), respectively. Age, male sex and trauma were associated with ARC with pooled OR (95% CI) of 0.95 (0.93–0.96), 2.36 (1.28–4.36), 2.60 (1.21–5.58), respectively. Limitations included variations in ARC definition, inclusion and exclusion criteria and studies design. In conclusion, ARC is prevalent in critically ill patients, especially those in the neurocritical care and trauma ICU population. Young age, male sex and trauma are risk factors for ARC in those with apparently normal renal function. Further research on optimal dosing of drugs in the setting of ARC is warranted. (Prospero registration: CRD42021246417).
New Preservative-Free Formulation for the Enhanced Ocular Bioavailability of Prostaglandin Analogues in Glaucoma
Authors: Alviset Gabriel , Corvis Yohann , Hammad Karim , Lemut Josiane , Maury Marc , Mignet Nathalie , Boudy Vincent
Published: February 2022

Glaucoma is a wide-spread eye disease caused by elevated intraocular pressure. Uncontrolled, this pressure may lead to damages to the optic nerve. Prostaglandin analogues, such as latanoprost and travoprost (which are water-insoluble active substances), are the most used class of active pharmaceutical ingredient. To administer them as eye drops, preservatives, such as benzalkonium chloride, are used as solubilizers. The latter is known to cause a local inflammation when used chronically and is not recommended for patients with ocular surface disorders. In this work, we sought to use polysorbate 80 (PS80) as a solubilizing agent simultaneously with sodium hyaluronate (NaHA) as a thickener and cytoprotective agent for the corneal surface. The first part of this study assessed the compatibility of the excipients with the active substance, using physicochemical methods such as spectra fluorescence and differential scanning calorimetry (DSC), as well as the solubilization mechanism of PS80 regarding prostaglandin analogues using nuclear magnetic resonance (NMR). The second part evaluated the stability of a formula candidate, its viscosity upon instillation, and its pharmacokinetic profile in rabbits as compared to the commercially approved medicine Travatan®. The results show that sodium hyaluronate is inert with respect to travoprost, while PS80 successfully solubilizes it, meaning that benzalkonium chloride is no longer required. Moreover, the pharmacokinetic profiles of the rabbits showed that the original formula described in the present study enhanced the ocular bioavailability of the drug, making it a promising product to control intraocular pressure with a potential reduced dosage of travoprost, therefore minimizing its related side effects.
Enhanced Photocatalytic Activity of TiO2 Thin Film Deposited by Reactive RF Sputtering under Oxygen-Rich Conditions
Authors: Ogawa Takaya , Zhao Yuekai , Okumura Hideyuki , Ishihara Keiichi N.
Published: February 2022

TiO2 thin films are promising as photocatalysts to decompose organic compounds. In this study, TiO2 thin films were deposited by reactive radio-frequency (RF) magnetron sputtering under various flow rates of oxygen and argon gas. The results show that the photocatalytic activity decreases as the oxygen-gas ratio is increased to 30% or less, while the activity increases under oxygen-rich conditions. It was observed that the crystal structure changed from anatase to a composite of anatase and rutile, where the oxygen-gas ratio during RF sputtering is more than 40%. Interestingly, the oxygen vacancy concentration increased under oxygen-rich conditions, where the oxygen-gas ratio is more than 40%. The sample prepared under the most enriched oxygen condition, 70%, among our experiments exhibited the highest concentration of oxygen vacancy and the highest photocatalytic activity. Both the oxygen vacancies and the composite of anatase and rutile structure in the TiO2 films deposited under oxygen-rich conditions are considered responsible for the enhanced photocatalysis.
Tachyon Behavior Due to Mass-State Transitions at Scattering Vertices
Authors: Fanchi John R.
Published: February 2022

A particle beam-thin foil scattering model is updated within the context of parametrized relativistic quantum theory (pRQT). This paper focuses on the creation, annihilation, and detection of tachyons when a beam of particles scatters off a thin foil. Improved calculation procedures and recent data are used to update model calculations for a pion-proton system.
Features of Chromosome Introgression from Gossypium barbadense L. into G. hirsutum L. during the Development of Alien Substitution Lines
Authors: Sanamyan Marina Feliksovna , Bobohujayev Shukhrat Umarovich , Abdukarimov Sharoffidin Sayfiddinovich , Makamov Abdusalom Khasanboyevich , Silkova Olga Gennadevna
Published: February 2022

The creation of G. barbadense L./G. hirsutum L. chromosome-substitution lines is an important method to transfer agronomically valuable traits from G. barbadense into G. hirsutum. In this study, 30 monosomic lines of G. hirsutum from the Cytogenetic Collection of Uzbekistan, created in the genotypic background of line L-458, were used in crosses with the G. barbadense line Pima 3-79 to create substitution lines. In the course of this work, new monosomic lines were identified for chromosome 12 and monotelodisome 6 of the Atsubgenome and for chromosomes 17, 21, and 22 of the Dtsubgenome using chromosome-specific SSR markers and a well-defined tester set of cotton translocation lines (USA). Compared to those in the F1 hybrids, a strong decrease in the crossing and setting rates was found in the BC1F1 backcross lines, with the substitution of chromosomes 2, 4, 6, 7, and 12 of the Atsubgenome and 17, 18, 21, and 22 of the Dtsubgenome. The F1 and BC1F1 offspring from interspecific crosses differed in their transmission of univalents. Despite the regular pairing of chromosomes and the high meiotic index, interspecific aneuploid hybrids were characterized by a decrease in pollen fertility, which may indicate hidden structural variability in these genomes that did not affect meiotic division. The identification of chromosomes using chromosome-specific SSR markers in the early stages of plant development has greatly accelerated the detection of monosomic plants. The analysis of morphobiological traits revealed that monosomic F1 hybrids were more similar to the donor line, while BC1F1 hybrids were more similar to the recurrent parent but also showed previously undetected traits.
Phytochemical Profiling and Assessment of Anticancer Activity of Leptocarpha rivularis Extracts Obtained from In Vitro Cultures
Authors: Rubio Julia , Arias Guisselle , Robles-Kelly Christian , Silva-Moreno Evelyn , Espinoza Luis , Carrasco Héctor , Olea Andrés F.
Published: February 2022

Plant cell culture is a source of plant material from which bioactive metabolites can be extracted. In this work, the in vitro propagation of Leptocarpha rivularis, an endemic Chilean shrub with anticancer activity, is described. Different media were tested and optimized for the introduction, propagation, and rooting steps of the micropropagation process. At the end of this process, 83% of plants were successfully acclimatized under greenhouse conditions. Callus induction from the internodal stem segment was performed using various combinations of phytohormones. Green-colored, friable, and non-organogenic callus was generated with a callus induction index higher than 90%. The chemical composition of extracts and callus, obtained from clonal plants, was assessed and the results indicate that the phytochemical profiles of extracts from micropropagated plants are like those found for plants collected from natural habitats, leptocarpine (LTC) being the major component. However, no LTC was detected in callus extract. HeLa and CoN cells, treated with LTC or extract of micropropagated plants, exhibit important diminution on cell viability and a drastic decrease in gene expression of IL-6 and mmp2, genes associated with carcinogenic activity. These effects are more important in cancer cells than in normal cells. Thus, micropropagated L. rivularis could be developed as a potential source of efficient antiproliferative agents.
Recent Advances in Novel Packaging Technologies for Shelf-Life Extension of Guava Fruits for Retaining Health Benefits for Longer Duration
Authors: Yadav Ajay , Kumar Nishant , Upadhyay Ashutosh , Fawole Olaniyi Amos , Mahawar Manoj Kumar , Jalgaonkar Kirti , Chandran Deepak , Rajalingam Sureshkumar , Zengin Gokhan , Kumar Manoj , Mekhemar Mohamed
Published: February 2022

Guava (Psidium guajava L.) fruit is also known as the apple of tropics, belongs to the family of genus Psidium, and is widely cultivated in tropical zones of the world. Recently, the importance of guava fruit has increased due to its inherent nutritional content, pleasant aroma, excellent flavor, and delicious taste. It is considered an excellent source of nutrients and phytochemicals. Guava is a climacteric fruit that continues to mature or ripen even after harvest, showing an increase in the rate of respiration and metabolic activities within a short period, leading to rapid senescence or spoilage of fruit. It has limitations in terms of commercialization due to short storage life after harvest and sensitivity to diseases and chilling injury during the storage period. Many postharvest technologies such as edible packaging, modified atmosphere packaging (MAP), composite packaging, controlled atmosphere packaging (CAP), antimicrobial/antifungal packaging, and nano packaging have been used to retard the chilling injury and enhance the keeping quality of guava fruits during the storage period to control respiration rate, reduce weight loss, minimize lipid oxidation, and maintain organoleptic properties. However, these packaging technologies have varied effects on the internal and external quality attributes of guava fruits. This review, therefore, discusses the physiology, mechanism of ripening, oxidation, and ethylene production of guava fruits. The review also discusses the packaging technologies and their effect on the postharvest characteristics of guava fruits during the storage period.
Absolute Quantification of Isoflavones in the Flowers of Pueraria lobata by qHNMR
Authors: Thapa Punam , Kim Hye Mi , Hong Joon-Pyo , Kim Ranhee , Paudel Sunil Babu , Choi Hyukjae , Jang Dae Sik , Nam Joo-Won
Published: February 2022

Pueraria lobata (Willd.) Ohwi. is a widely used medicinal plant in Korea, China, and Japan. The flower of P. lobata (Puerariae Flos) contains various bioactive substances such as triterpenoidal saponins and isoflavonoids. In this study, we developed a quantitative analysis of the isoflavones of Puerariae Flos by quantitative proton nuclear magnetic resonance (qHNMR) spectroscopy using the internal calibrant (IC). From the qHNMR results, the isoflavone content was found to be 7.99% and 10.57% for the MeOH sonication extract (PLs) and the MeOH reflux extract (PLr) of Puerariae Flos, respectively. The quantified isoflavone content was validated using the conventional analytical method, high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The present study shows that validated qHNMR spectroscopy is a reliable method for quantifying and standardizing the isoflavone content in Puerariae Flos.
The Passage of H2O2 from Chloroplasts to Their Associated Nucleus during Retrograde Signalling: Reflections on the Role of the Nuclear Envelope
Authors: Breeze Emily , Mullineaux Philip M.
Published: February 2022

The response of chloroplasts to adverse environmental cues, principally increases in light intensity, stimulates chloroplast-to-nucleus retrograde signalling, which leads to the induction of immediate protective responses and longer-term acclimation. Hydrogen peroxide (H2O2), generated during photosynthesis, is proposed to both initiate and transduce a retrograde signal in response to photoinhibitory light intensities. Signalling specificity achieved by chloroplast-sourced H2O2 for signal transduction may be dependent upon the oft-observed close association of a proportion of these organelles with the nucleus. In this review, we consider more precisely the nature of the close association between a chloroplast appressed to the nucleus and the requirement for H2O2 to cross both the double membranes of the chloroplast and nuclear envelopes. Of particular relevance is that the endoplasmic reticulum (ER) has close physical contact with chloroplasts and is contiguous with the nuclear envelope. Therefore, the perinuclear space, which transducing H2O2 molecules would have to cross, may have an oxidising environment the same as the ER lumen. Based on studies in animal cells, the ER lumen may be a significant source of H2O2 in plant cells arising from the oxidative folding of proteins. If this is the case, then there is potential for the ER lumen/perinuclear space to be an important location to modify chloroplast-to-nucleus H2O2 signal transduction and thereby introduce modulation of it by additional different environmental cues. These would include for example, heat stress and pathogen infection, which induce the unfolded protein response characterised by an increased H2O2 level in the ER lumen.