bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the Variability of Essential Oil Composition in Different Accessions of Bunium persicum Collected from Different Temperate Micro-Climates
Authors: Khan Mudasir Hafiz , Dar Niyaz Ahmad , Alie Bashir Ahmad , Dar Sher Ahmad , Lone Ajaz Ahmad , Mir Ghulam Hassan , Fayaz Uzma , Ali Sajad , Tyagi Anshika , El-Sheikh Mohamed A. , Alansi Saleh
Published: March 2023

The present investigation was performed to evaluate the variability of the essential oil composition present in the seed extract of Kala zeera (Bunium persicum Bioss.) obtained from different geographical zones of Northwestern-Himalayan using Gas Chromatography-Mass Spectrum (GC-MS). The results of the GC-MS analysis revealed significant differences in the essential oil content. Significant variability was observed in the chemical constituents of the essential oils mainly for p-cymene, D-limonene, Gamma-terpinene, Cumic aldehyde and 1, 4-p-menthadien-7-al. Among these compounds, the highest average percentage across the locations was observed for gamma-terpinene (32.08%) which was followed by cumic aldehyde (25.07%), and 1, 4-p-menthadien-7-al (15.45%). Principal component analysis (PCA) also grouped the 4 highly significant compounds i.e., p-Cymene, Gamma-Terpinene, Cumic aldehyde, and 1,4-p-Menthadien-7-al into same cluster which are mainly distributed in Shalimar Kalazeera-1, and Atholi Kishtwar zones. The highest value of gamma-terpinene was recorded in Atholi accession (40.66%). However, among climatic zones Zabarwan Srinagar and Shalimar Kalazeera-1 was found to have highly positive significant correlation (0.99). The cophenetic correlation coefficient (c) was found to be 0.8334 during hierarchical clustering for 12 essential oil compounds showing that our results are highly correlated. Network analysis also showed the overlapping pattern and similar interaction between the 12 compounds as shown by hierarchical clustering analysis. From the results, it could be concluded that existence of variability among the various bioactive compounds of B. persicum which are probably to be incorporated to the potential list of drugs and may serve as good genetic source for various modern breeding programs.
Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention
Authors: Shamim Md Abdullah , Shahid Ayaz , Sardar Pabitra K. , Yeung Steven , Reyes Jeremiah , Kim Jenny , Parsa Cyrus , Orlando Robert , Wang Jeffrey , Kelly Kristen M. , Meyskens Frank L. , Andresen Bradley T. , Huang Ying
Published: March 2023

The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug–lipid–surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.
Design Optimization and Characterization with Fabrication of Nanomaterials-Based Photo Diode Cell for Subretinal Implant Application
Authors: Moorthy Vijai M. , Rathnasami Joseph D. , Srivastava Viranjay M.
Published: March 2023

An ultrathin nano photodiode array fabricated in a flexible substrate can be an ideal therapeutic replacement for degenerated photoreceptor cells damaged by Age-related Macula Degeneration (AMD) and Retinitis Pigmentosa (RP), such as retinal infections. Silicon-based photodiode arrays have been attempted as artificial retinas. Considering the difficulties caused by hard silicon subretinal implants, researchers have diverted their attention towards organic photovoltaic cells-based subretinal implants. Indium-Tin Oxide (ITO) has been a favorite choice as an anode electrode. A mix of poly(3-hexylthiophene) and [6,6]-phenyl C61-butyric acid methyleste (P3HT: PCBM) has been utilized as an active layer in such nanomaterial-based subretinal implants. Though encouraging results have been obtained during the trial of such retinal implants, the need to replace ITO with a suitable transparent conductive electrode will be a suitable substitute. Further, conjugated polymers have been used as active layers in such photodiodes and have shown delamination in the retinal space over time despite their biocompatibility. This research attempted to fabricate and characterize Bulk Hetero Junction (BHJ) based Nano Photo Diode (NPD) utilizing Graphene–polyethylene terephthalate (G–PET)/semiconducting Single-Wall Carbon Nano Tubes (s-SWCNT): fullerene (C60) blend/aluminium (Al) structure to determine the issues in the development of subretinal prosthesis. An effective design approach adopted in this analysis has resulted in developing an NPD with an Efficiency of 10.1% in a non-ITO-driven NPD structure. Additionally, the results show that the efficiency can be further improved by increasing active layer thickness.
Ball-Mill-Inspired Durable Triboelectric Nanogenerator for Wind Energy Collecting and Speed Monitoring
Authors: Qin Qinghao , Cao Xia , Wang Ning
Published: March 2023

Triboelectric nanogenerators have attracted extensive attention in energy harvesting due to its light weight, low cost, high flexibility, and diversity of function. However, deterioration in terms of mechanical durability and electrical stability of the triboelectric interface during operation, which are the results of material abrasion, severely limits their practical applications. In this paper, a durable triboelectric nanogenerator inspired by a ball mill was designed by using metal balls in hollow drums as carriers for charge generation and transfer. Composite nanofibers were deposited onto the balls, increasing the triboelectrification with the interdigital electrodes in the inner surface of the drum for higher output and electrostatic repulsion to each other for lower wear. Such a rolling design cannot only increase mechanical durability and maintenance convenience, where the filler can be easily replaced and recycled but also collect wind power with the decreased wearing of materials and sound efficiency in comparison with the typical rotation TENG. In addition, the short circuit current shows a strong linear relationship with the rotation speed in a wide range, which can be used to detect wind speed, thus showing potential applications in distributed energy conversion and self-powered environmental monitoring systems.
Novel Sol-Gel Route to Prepare Eu3+-Doped 80SiO2-20NaGdF4 Oxyfluoride Glass-Ceramic for Photonic Device Applications
Authors: Cruz María Eugenia , Ngoc Lam Tran Thi , Chiasera Alessandro , Durán Alicia , Fernandez Joaquín , Balda Rolindes , Castro Yolanda
Published: March 2023

Oxyfluoride glass-ceramics (OxGCs) with the molar composition 80SiO2-20(1.5Eu3+: NaGdF4) were prepared with sol-gel following the “pre-crystallised nanoparticles route” with promising optical results. The preparation of 1.5 mol % Eu3+-doped NaGdF4 nanoparticles, named 1.5Eu3+: NaGdF4, was optimised and characterised using XRD, FTIR and HRTEM. The structural characterisation of 80SiO2-20(1.5Eu3+: NaGdF4) OxGCs prepared from these nanoparticles’ suspension was performed by XRD and FTIR revealing the presence of hexagonal and orthorhombic NaGdF4 crystalline phases. The optical properties of both nanoparticles’ phases and the related OxGCs were studied by measuring the emission and excitation spectra together with the lifetimes of the 5D0 state. The emission spectra obtained by exciting the Eu3+-O2− charge transfer band showed similar features in both cases corresponding the higher emission intensity to the 5D0→7F2 transition that indicates a non-centrosymmetric site for Eu3+ ions. Moreover, time-resolved fluorescence line-narrowed emission spectra were performed at a low temperature in OxGCs to obtain information about the site symmetry of Eu3+ in this matrix. The results show that this processing method is promising for preparing transparent OxGCs coatings for photonic applications.
Mechanism of Double-Diffusive Convection on Peristaltic Transport of Thermally Radiative Williamson Nanomaterials with Slip Boundaries and Induced Magnetic Field: A Bio-Nanoengineering Model
Authors: Akram Safia , Athar Maria , Saeed Khalid , Razia Alia , Muhammad Taseer , Alghamdi Huda Ahmed
Published: March 2023

The present work has mathematically modeled the peristaltic flow in nanofluid by using thermal radiation, induced a magnetic field, double-diffusive convection, and slip boundary conditions in an asymmetric channel. Peristalsis propagates the flow in an asymmetric channel. Using the linear mathematical link, the rheological equations are translated from fixed to wave frames. Next, the rheological equations are converted to nondimensional forms with the help of dimensionless variables. Further, the flow evaluation is determined under two scientific assumptions: a finite Reynolds number and a long wavelength. Mathematica software is used to solve the numerical value of rheological equations. Lastly, the impact of prominent hydromechanical parameters on trapping, velocity, concentration, magnetic force function, nanoparticle volume fraction, temperature, pressure gradient, and pressure rise are evaluated graphically.
An Analysis of the Toxicity, Antioxidant, and Anti-Cancer Activity of Cinnamon Silver Nanoparticles in Comparison with Extracts and Fractions of Cinnamomum Cassia at Normal and Cancer Cell Levels
Authors: El-Baz Y. G. , Moustafa A. , Ali M. A. , El-Desoky G. E. , Wabaidur S. M. , Faisal M. M.
Published: March 2023

In this work, the extract of cinnamon bark was used for the green synthesis of cinnamon-Ag nanoparticles (CNPs) and other cinnamon samples, including ethanolic (EE) and aqueous (CE) extracts, chloroform (CF), ethyl acetate (EF), and methanol (MF) fractions. The polyphenol (PC) and flavonoid (FC) contents in all the cinnamon samples were determined. The synthesized CNPs were tested for the antioxidant activity (as DPPH radical scavenging percentage) in Bj-1 normal cells and HepG-2 cancer cells. Several antioxidant enzymes, including biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH), were verified for their effects on the viability and cytotoxicity of normal and cancer cells. The anti-cancer activity depended on apoptosis marker protein levels (Caspase3, P53, Bax, and Pcl2) in normal and cancerous cells. The obtained data showed higher PC and FC contents in CE samples, while CF showed the lowest levels. The IC50 values of all investigated samples were higher, while their antioxidant activities were lower than those of vitamin C (5.4 g/mL). The CNPs showed lower IC50 value (55.6 µg/mL), whereas the antioxidant activity inside or outside the Bj-1 or HepG-2 was found to be higher compared with other samples. All samples execrated a dose-dependent cytotoxicity by decreasing the cells’ viability percent of Bj-1 and HepG-2. Similarly, the anti-proliferative potency of CNPs on Bj-1 or HepG-2 at different concentrations was more effective than that of other samples. Higher concentrations of the CNPs (16 g/mL) showed greater cell death in Bj-1 (25.68%) and HepG-2 (29.49%), indicating powerful anti-cancer properties of the nanomaterials. After 48 h of CNPs treatment, both Bj-1 and HepG-2 showed significant increases in biomarker enzyme activities and reduced glutathione compared with other treated samples or untreated controls (p < 0.05). The anti-cancer biomarker activities of Caspas-3, P53, Bax, and Bcl-2 levels were significantly changed in Bj-1 or HepG-2 cells. The cinnamon samples were significantly increased in Caspase-3, Bax, and P53, while there were decreased Bcl-2 levels compared with control.
Humidity Sensing Properties of (In+Nb) Doped HfO2 Ceramics
Authors: Yao Jiahao , Wang Jingsong , Cao Wenjun , Li Li , Luo Mingxiang , Wang Chunchang
Published: March 2023

(In+Nb) co-doped HfO2 ceramics, Hf1-x(In0.5Nb0.5)xO2 (x = 0, 0.005, 0.05, and 0.1), were prepared via a solid-state reaction method. Dielectric measurements reveal that the environmental moisture has an obvious influence on the dielectric properties of the samples. The best humidity response was found in a sample with the doping level of x = 0.005. This sample was therefore selected as a model sample to further investigate its humidity properties. In doing so, nanosized particles of Hf0.995(In0.5Nb0.5)0.005O2 were fabricated via a hydrothermal method and the humidity sensing properties of this material were studied in the relative humidity range of 11–94% based on impedance sensor. Our results show that the material exhibits a large impedance change of nearly four orders of magnitude over the tested humidity range. It was argued that the humidity-sensing properties were related to the defects created by doping, which improves the adsorption capacity for water molecules.
Associations between Plasma Essential Metals Levels and the Risks of All-Cause Mortality and Cardiovascular Disease Mortality among Individuals with Type 2 Diabetes
Authors: Li Zhaoyang , Wang Ruixin , Long Tengfei , Xu Yali , Guo Huan , Zhang Xiaomin , He Meian
Published: March 2023

Epidemiological evidence regarding the possible link between multiple essential metals levels and all-cause mortality and cardiovascular disease (CVD) mortality among type 2 diabetes (T2D) patients is sparse. Here, we aimed to evaluate the longitudinal associations between 11 essential metals levels in plasma and all-cause mortality and CVD mortality among T2D patients. Our study included 5278 T2D patients from the Dongfeng–Tongji cohort. LASSO penalized regression analysis was used to select the all-cause and CVD mortality-associated metals from 11 essential metals (iron, copper, zinc, selenium, manganese, molybdenum, vanadium, cobalt, chromium, nickel, and tin) measured in plasma. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With a median follow-up of 9.8 years, 890 deaths were documented, including 312 deaths of CVD. LASSO regression models and the multiple-metals model revealed that plasma iron and selenium were negatively associated with all-cause mortality (HR: 0.83; 95%CI: 0.70, 0.98; HR: 0.60; 95%CI: 0.46, 0.77), whereas copper was positively associated with all-cause mortality (HR: 1.60; 95%CI: 1.30, 1.97). Only plasma iron has been significantly associated with decreased risk of CVD mortality (HR: 0.61; 95%CI: 0.49, 0.78). The dose-response curves for the association between copper levels and all-cause mortality followed a J shape (Pfor nonlinear = 0.01). Our study highlights the close relationships between essential metals elements (iron, selenium, and copper) and all-cause and CVD mortality among diabetic patients.
Rutin, a Flavonoid Compound Derived from Garlic, as a Potential Immunomodulatory and Anti-Inflammatory Agent against Murine Schistosomiasis mansoni
Authors: Hamad Rabab S.
Published: March 2023

Schistosomiasis is a tropical disease caused by trematode worms. The inflammatory response of the host to schistosome eggs leads to formation of granuloma in the liver and intestine. Praziquantel (PZQ) is still an effective treatment for schistosomiasis, however resistance development may reduce its efficacy. The current study investigated the possible immunomodulatory and anti-inflammatory action of rutin, a natural flavonoid compound isolated from garlic, on liver fibrotic markers in mice infected with S. mansoni in comparison to PZQ. Male albino CD1 mice were infected with 100 ± 2 S. mansoni cercariae/mouse and treated with garlic, rutin, or PZQ. At the end of the experiment, the liver and intestines were harvested for parasitological and histological assessment and to analyze the proinflammatory cytokine. Rutin significantly affects the pathological alterations caused by Schistosoma in the liver. This may be partially explained by a decrease in the number of eggs trapped in the tissues of the liver and a modification in the serum levels of certain cytokines, which are implicated in the formation of Schistosoma granuloma. In conclusion, rutin has strong anti-schistosome properties in vivo, raising the possibility that rutin might be further investigated as a therapy for S. mansoni.
Involvement of Periodontal Disease in the Pathogenesis and Exacerbation of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis: A Review
Authors: Kobayashi Takashi , Iwaki Michihiro , Nogami Asako , Honda Yasushi , Ogawa Yuji , Imajo Kento , Saito Satoru , Nakajima Atsushi , Yoneda Masato
Published: March 2023

The increasing incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), along with global lifestyle changes, requires further in-depth research to elucidate the mechanisms and develop new treatment strategies. In addition, the number of patients with periodontal disease has increased recently, suggesting that periodontal disease is sometimes associated with systemic conditions. In this review, we summarize recent studies linking periodontal disease and NAFLD, the concept of the mouth–gut–liver axis, oral and intestinal microbiota, and liver disease. We suggest new research directions toward a detailed mechanistic understanding and novel targets for treatment and prevention. Forty years have passed since the concepts of NAFLD and NASH were first proposed. however, no effective prevention or treatment has been established. We also found that the pathogenesis of NAFLD/NASH is not limited to liver-related diseases but has been reported to be associated with various systemic diseases and an increasing number of causes of death. In addition, changes in the intestinal microbiota have been shown to be a risk factor for periodontal diseases, such as atherosclerosis, diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, and obesity.
Low-Income Families’ Direct Participation in Food-Systems Innovation to Promote Healthy Food Behaviors
Authors: Katre Aparna , Raddatz Brianna
Published: March 2023

Low-income families, especially those who reside in food deserts, face significant systemic barriers regarding their ability to access affordable and nutritious food. The food behaviors exhibited by low-income families are a reflection of the shortcomings of the built environment and conventional food system. Policy and public-health initiatives to improve food security have, thus far, failed to deliver interventions that simultaneously address multiple pillars of food security. Centering the voices of the marginalized and their place-based knowledge may result in the development of food-access solutions that are a much better fit for the population that they intend to serve. Community-based participatory research has emerged as a solution to better meet the needs of communities in food-systems innovation, but little is known about the extent to which direct participation improves nutritional outcomes. The purpose of this research is to answer the following question: how can food-access solutions authentically engage marginalized community members in food-system innovation, and if participation is related to changes in their food behaviors, how is it related? This action research project leveraged a mixed-methods approach to analyze nutritional outcomes and define the nature of participation for 25 low-income families who reside in a food desert. Our findings suggest that nutritional outcomes improve when major barriers to healthy food consumption are addressed, for example, time, education, and transportation. Furthermore, participation in social innovations can be characterized by the nature of involvement as either a producer or consumer, actively or inactively involved. We conclude that when marginalized communities are at the center of food-systems innovation, individuals self-select their level of participation, and when primary barriers are addressed, deeper participation in food-systems innovation is associated with positive changes in healthy food behaviors.
Metabolically Healthy Overweight and Obesity, Transition to Metabolically Unhealthy Status and Cognitive Function: Results from the Framingham Offspring Study
Authors: Kouvari Matina , M. D’Cunha Nathan , Tsiampalis Thomas , Zec Manja , Sergi Domenico , Travica Nikolaj , Marx Wolfgang , McKune Andrew J. , Panagiotakos Demosthenes B. , Naumovski Nenad
Published: March 2023

Aims: To evaluate the association between metabolically healthy overweight/obesity (MHO) status and longitudinal cognitive function while also considering the stability of the condition. Methods: In total, 2892 participants (mean age 60.7 (9.4) years) from Framingham Offspring Study completed health assessments every four years since 1971. Neuropsychological testing was repeated every four years starting from 1999 (Exam 7) to 2014 (Exam 9) (mean follow-up: 12.9 (3.5) years). Standardized neuropsychological tests were constructed into three factor scores (general cognitive performance, memory, processing speed/executive function). Healthy metabolic status was defined as the absence of all NCEP ATP III (2005) criteria (excluding waist circumference). MHO participants who scored positively for one or more of NCEP ATPIII parameters in the follow-up period were defined as unresilient MHO. Results: No significant difference on the change in cognitive function over time was observed between MHO and metabolically healthy normal weight (MHN) individuals (all p > 0.05). However, a lower processing speed/executive functioning scale score was observed in unresilient MHO participants compared to resilient MHO participants (β = −0.76; 95% CI = −1.44, −0.08; p = 0.030). Conclusions: Retaining a healthy metabolic status over time represents a more important discriminant in shaping cognitive function compared to body weight alone.
Uncovering Barriers and Facilitators of Weight Loss and Weight Loss Maintenance: Insights from Qualitative Research
Authors: Tay Audrey , Hoeksema Hannah , Murphy Rinki
Published: March 2023

Long-term weight loss maintenance is often difficult to achieve. This review analysed qualitative data on self-perceived barriers and facilitators of weight loss and weight loss maintenance among weight loss intervention participants. A literature search was conducted using electronic databases. Qualitative studies written in English and published between 2011–2021 were eligible for inclusion if they explored the perspectives and experiences of individuals who received standardised dietary and behavioural support for weight loss. Studies were excluded if weight loss was achieved through self-directed methods, only increasing physical activity, or surgical or pharmacological interventions. Fourteen studies were included, totaling 501 participants from six countries. Thematic analysis was used to identify four aggregate themes: internal factors (i.e., motivation and self-efficacy), programme-specific factors (i.e., the intervention diet), social factors (i.e., supporters and saboteurs), and environmental factors (i.e., an obesogenic environment). Our findings demonstrate that internal, social, and environmental factors all influence weight loss success, as well as the acceptability of the weight loss intervention. Future interventions may be more successful if they prioritise participant acceptability and engagement by, for example, providing tailored interventions, a structured relapse management plan, strategies to enhance autonomous motivation and emotional self-regulation, and extended contact during weight loss maintenance.
TRPA1 Agonists and Bladder Nociception in Female Rats Suggest Potential for Nutraceutical Benefit from Cinnamon
Authors: Ness Timothy J. , Babi Amer , Ness Madeline E. , DeWitte Cary
Published: March 2023

TRPA1-related drugs alter sensation, particularly in conditions of inflammation. To further characterize the role of these drugs in bladder sensation, the TRPA1 agonist cinnamaldehyde (CMA) and oral true cinnamon spice were examined in preclinical models of bladder pain. Female adult rats, with and without acute zymosan-induced cystitis, were anesthetized and visceromotor (VMR) and cystometric responses to urinary bladder distension (UBD) were determined following either the intravesical administration of CMA/vehicle solutions or the oral administration of true cinnamon/vehicle. ELISA measures of bladder TRPA1 content were also determined. Acute cystitis resulted in increases in bladder TRPA1 content and produced an increased vigor of the VMRs to UBD and a lowering of micturition volume thresholds for activation of a micturition response. Intravesical CMA produced a robust inhibition of VMRs to UBD in rats with cystitis but not in those without. Micturition volume thresholds were lowered by CMA in rats without cystitis but had no additional effect in rats with cystitis. Oral cinnamon also produced a robust inhibition of VMRs to UBD in rats with cystitis and a mild augmentation of VMRs to UBD in rats without cystitis. A potentially analgesic effect of the spice, true cinnamon, in the treatment of the pain of acute cystitis was suggested by these preclinical studies. Human studies are indicated.
Exposure to Doxorubicin Modulates the Cardiac Response to Isoproterenol in Male and Female Mice
Authors: Agostinucci Kevin , Grant Marianne K. O. , Melaku Wongel , Nair Chandini , Zordoky Beshay N.
Published: March 2023

Sex is a salient risk factor in the development of doxorubicin-induced cardiotoxicity. Sex differences in the heart’s ability to respond to hypertrophic stimuli in doxorubicin-exposed animals have not been reported. We identified the sexual dimorphic effects of isoproterenol in mice pre-exposed to doxorubicin. Male and female intact or gonadectomized C57BL/6N mice underwent five weekly intraperitoneal injections of 4 mg/kg doxorubicin followed by a five-week recovery period. Fourteen days of subcutaneous isoproterenol injections (10 mg/kg/day) were administered after the recovery period. Echocardiography was used to assess heart function one and five weeks after the last doxorubicin injection and on the fourteenth day of isoproterenol treatment. Thereafter, mice were euthanized, and the hearts were weighed and processed for histopathology and gene expression analysis. Doxorubicin did not produce overt cardiac dysfunction in male or female mice before starting isoproterenol treatment. The chronotropic response to a single isoproterenol injection was blunted by doxorubicin, but the inotropic response was maintained in both males and females. Pre-exposure to doxorubicin caused cardiac atrophy in both control and isoproterenol-treated male mice but not in female mice. Counterintuitively, pre-exposure to doxorubicin abrogated isoproterenol-induced cardiac fibrosis. However, there were no sex differences in the expression of markers of pathological hypertrophy, fibrosis, or inflammation. Gonadectomy did not reverse the sexually dimorphic effects of doxorubicin. Additionally, pre-exposure to doxorubicin abrogated the hypertrophic response to isoproterenol in castrated male mice but not in ovariectomized female mice. Therefore, pre-exposure to doxorubicin caused male-specific cardiac atrophy that persisted after isoproterenol treatment, which could not be prevented by gonadectomy.
Melatonin Prescription in Children and Adolescents in Relation to Body Weight and Age
Authors: Kimland Elin E. , Dahlén Elin , Martikainen Jari , Célind Jimmy , Kindblom Jenny M.
Published: March 2023

The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based BMI Epidemiology Study Gothenburg cohort has weight available from school health care records, and information on melatonin prescription through linkage with high-quality national registers. We included prescriptions of melatonin to individuals below 18 years of age where a weight measurement not earlier than three months before, or later than six months after the dispensing date, was available (n = 1554). Similar maximum doses were prescribed to individuals with overweight orobesity as to individuals with normal weight, and to individuals below and above 9 years of age. Age and weight only explained a marginal part of the variance in maximum dose, but were inversely associated and explained a substantial part of the variance in maximum dose per kg. As a result, individuals overweight or with obesity, or age above 9 years, received lower maximum dose per kg of body weight, compared with individuals with normal weight or below 9 years of age. Thus, the prescribed melatonin dose to individuals under 18 years of age is not primarily informed by body weight or age, resulting in substantial differences in prescribed dose per kg of body weight across BMI and age distribution.
Polymeric Gel Systems Cytotoxicity and Drug Release as Key Features for their Effective Application in Various Fields of Addressed Pharmaceuticals Delivery
Authors: Smagina Veronika , Yudaev Pavel , Kuskov Andrey , Chistyakov Evgeniy
Published: March 2023

Modified polymeric gels, including nanogels, which play not only the role of a bioinert matrix, but also perform regulatory, catalytic, and transport functions due to the active fragments introduced into them, can significantly advance the solution to the problem of targeted drug delivery in an organism. This will significantly reduce the toxicity of used pharmaceuticals and expand the range of their therapeutic, diagnostic, and medical application. This review presents a comparative description of gels based on synthetic and natural polymers intended for pharmaceutical-targeted drug delivery in the field of therapy of inflammatory and infectious diseases, dentistry, ophthalmology, oncology, dermatology, rheumatology, neurology, and the treatment of intestinal diseases. An analysis was made of most actual sources published for 2021–2022. The review is focused on the comparative characteristics of polymer gels in terms of their toxicity to cells and the release rate of drugs from nano-sized hydrogel systems, which are crucial initial features for their further possible application in mentioned areas of biomedicine. Different proposed mechanisms of drug release from gels depending on their structure, composition, and application are summarized and presented. The review may be useful for medical professionals, and pharmacologists dealing with the development of novel drug delivery vehicles.
Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo
Authors: Panchuk Rostyslav , Skorokhyd Nadiya , Chumak Vira , Lehka Lilya , Kosiakova Halyna , Horid’ko Tetyana , Hudz Iehor , Hula Nadiya , Riabtseva Anna , Mitina Nataliya , Zaichenko Alexander , Heffeter Petra , Berger Walter , Stoika Rostyslav
Published: March 2023

This study reports a dose-dependent pro-apoptotic action of synthetic cannabimimetic N-stearoylethanolamine (NSE) on diverse cancer cell lines, including multidrug-resistant models. No antioxidant or cytoprotective effects of NSE were found when it was applied together with doxorubicin. A complex of NSE with the polymeric carrier poly(5-(tert-butylperoxy)-5-methyl-1-hexen-3-yn-co-glycidyl methacrylate)-graft-PEG was synthesized. Co-immobilization of NSE and doxorubicin on this carrier led to a 2-10-fold enhancement of the anticancer activity, particularly, against drug-resistant cells overexpressing ABCC1 and ABCB1. This effect might be caused by accelerated nuclear accumulation of doxorubicin in cancer cells, which led to the activation of the caspase cascade, revealed by Western blot analysis. The NSE-containing polymeric carrier was also able to significantly enhance the therapeutic activity of doxorubicin in mice with implanted NK/Ly lymphoma or L1210 leukemia, leading to the complete eradication of these malignancies. Simultaneously, loading to the carrier prevented doxorubicin-induced elevation of AST and ALT as well as leukopenia in healthy Balb/c mice. Thus, a unique bi-functionality of the novel pharmaceutical formulation of NSE was revealed. It enhanced doxorubicin-induced apoptosis in cancer cells in vitro and promoted its anticancer activity against lymphoma and leukemia models in vivo. Simultaneously, it was very well tolerated preventing frequently observed doxorubicin-associated adverse effects.
Development of Small Molecules Targeting α-Synuclein Aggregation: A Promising Strategy to Treat Parkinson’s Disease
Authors: Peña-Díaz Samuel , García-Pardo Javier , Ventura Salvador
Published: March 2023

Parkinson’s disease, the second most common neurodegenerative disorder worldwide, is characterized by the accumulation of protein deposits in the dopaminergic neurons. These deposits are primarily composed of aggregated forms of α-Synuclein (α-Syn). Despite the extensive research on this disease, only symptomatic treatments are currently available. However, in recent years, several compounds, mainly of an aromatic character, targeting α-Syn self-assembly and amyloid formation have been identified. These compounds, discovered by different approaches, are chemically diverse and exhibit a plethora of mechanisms of action. This work aims to provide a historical overview of the physiopathology and molecular aspects associated with Parkinson’s disease and the current trends in small compound development to target α-Syn aggregation. Although these molecules are still under development, they constitute an important step toward discovering effective anti-aggregational therapies for Parkinson’s disease.
Prevalence, Risk, and Challenges of Extemporaneous Preparation for Pediatric Patients in Developing Nations: A Review
Authors: Yuliani Sri Hartati , Putri Dina Christin Ayuning , Virginia Dita Maria , Gani Michael Raharja , Riswanto Florentinus Dika Octa
Published: March 2023

Extemporaneous preparations are still widely prescribed for pediatric patients with special treatments of certain doses and/or combinations of drugs. Several problems related to extemporaneous preparations have been linked to the incidence of adverse events or a lack of therapeutic effectiveness. Developing nations are facing the challenges of compounding practices. The prevalence of compounded medication in developing nations must be explored to determine the urgency of compounding practices. Furthermore, the risks and challenges are described and explained through investigation and collection of numerous scientific articles from reputable databases, including Web of Science, Scopus, and PubMed. Pediatric patients need compounded medication related to the appropriate dosage form and dosage adjustment. Notably, it is important to observe extemporaneous preparations in order to provide patient-oriented medication.
Influence of Large-Aperture Output Wavefront Distribution on Focal Spot in High-Power Laser Facility
Authors: Li Jiamei , Yu Hui , Li Dawei , Wang Li , Zhang Junyong , Zhou Qiong , Lv Fengnian , Lu Xingqiang
Published: March 2023

To improve the focal spot quality, the output wavefront of the Shenguang-II Upgrade facility is divided into four types based on the spatial frequency and division band of power spectral density. The influence of each on the focal spot was quantitatively studied, and the results indicate that the spatial profile, energy concentration, and peak intensity of the focal spot are mainly affected by low-spatial-frequency, and the relative intensity of the sidelobes is greatly affected by both the low- and mid-spatial counterparts. The peak-to-valley value of the wavefront of the Shenguang-II Upgrade should not exceed 2.27λ under the requirement that 50% of the energy is enclosed within 3 times the diffraction limit (DL), and it should be less than 2.45λ under the requirement that 95% is within 10DL. Meanwhile, the Strehl ratio dropped to within 0.2 under these conditions. These results can be applied to focal quality improvement in designing an adaptive optical system, optical element processing, as well as focal spot prediction in high-power laser facilities.
Moving Away from 12:12; the Effect of Different Photoperiods on Biomass Yield and Cannabinoids in Medicinal Cannabis
Authors: Peterswald Tyson James , Mieog Jos Cornelis , Azman Halimi Razlin , Magner Nelson Joel , Trebilco Amy , Kretzschmar Tobias , Purdy Sarah Jane
Published: March 2023

The standard practice to initiate flowering in medicinal cannabis involves reducing the photoperiod from a long-day period to an equal duration cycle of 12 h light (12L)/12 h dark (12D). This method reflects the short-day flowering dependence of many cannabis varieties but may not be optimal for all. We sought to identify the effect of nine different flowering photoperiod treatments on the biomass yield and cannabinoid concentration of three medicinal cannabis varieties. The first, “Cannatonic”, was a high cannabidiol (CBD)-accumulating line, whereas the other two, “Northern Lights” and “Hindu Kush”, were high Δ9-tetrahydrocannabinol (THC) accumulators. The nine treatments tested, following 18 days under 18 h light/6 h dark following cloning and propagation included a standard 12L:12D period, a shortened period of 10L:14D, and a lengthened period of 14L:10D. The other six treatments started in one of the aforementioned and then 28 days later (mid-way through flowering) were switched to one of the other treatments, thus causing either an increase of 2 or 4 h, or a decrease of 2 or 4 h. Measured parameters included the timing of reproductive development; the dry weight flower yield; and the % dry weight of the main target cannabinoids, CBD and THC, from which the total g cannabinoid per plant was calculated. Flower biomass yields were highest for all lines when treatments started with 14L:10D; however, in the two THC lines, a static 14L:10D photoperiod caused a significant decline in THC concentration. Conversely, in Cannatonic, all treatments starting with 14L:10D led to a significant increase in the CBD concentration, which led to a 50–100% increase in total CBD yield. The results show that the assumption that a 12L:12D photoperiod is optimal for all lines is incorrect as, in some lines, yields can be greatly increased by a lengthened light period during flowering.
Phytochemical Composition and Biological Activities of Extracts from Early, Mature, and Germinated Somatic Embryos of Cotyledon orbiculata L.
Authors: Zengin Gokhan , Cziáky Zoltán , Jekő József , Kang Kyung Won , Lorenzo José Manuel , Sivanesan Iyyakkannu
Published: March 2023

Cotyledon orbiculata L. (Crassulaceae)—round-leafed navelwort—is used worldwide as a potted ornamental plant, and it is also used in South African traditional medicine. The current work aims to assess the influence of plant growth regulators (PGR) on somatic embryogenesis (SE) in C. orbiculata; compare the metabolite profile in early, mature, and germinated somatic embryos (SoEs) by utilizing ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS); and determine the antioxidant and enzyme inhibitory potentials of SoEs. A maximum SoE induction rate of 97.2% and a mean number of SoEs per C. orbiculata leaf explant of 35.8 were achieved on Murashige and Skoog (MS) medium with 25 µM 2,4-Dichlorophenoxyacetic acid and 2.2 µM 1-phenyl-3-(1,2,3,-thiadiazol-5-yl)urea. The globular SoEs were found to mature and germinate best on MS medium with gibberellic acid (4 µM). The germinated SoE extract had the highest amounts of both total phenolics (32.90 mg gallic acid equivalent/g extract) and flavonoids (1.45 mg rutin equivalent/g extract). Phytochemical evaluation of SoE extracts by UHPLC-MS/MS reveals the presence of three new compounds in mature and germinated SoEs. Among the SoE extracts tested, germinated SoE extract exhibited the most potent antioxidant activity, followed by early and mature somatic embryos. The mature SoE extract showed the best acetylcholinesterase inhibitory activity. The SE protocol established for C. orbiculata can be used for the production of biologically active compounds, mass multiplication, and conservation of this important species.
Seed Storage Physiology of Lophomyrtus and Neomyrtus, Two Threatened Myrtaceae Genera Endemic to New Zealand
Authors: van der Walt Karin , Nadarajan Jayanthi
Published: March 2023

There is no published information on the seed germination or seed storage physiology of Lophomyrtus bullata, Lophomyrtus obcordata, and Neomyrtus pedunculata. This lack of information is hampering conservation efforts of these critically endangered species. This study investigated the seed morphology, seed germination requirements, and long-term seed storage methods for all three species. The impact of desiccation, desiccation and freezing, as well as desiccation plus storage at 5 °C, −18 °C, and −196 °C on seed viability (germination) and seedling vigour was assessed. Fatty acid profiles were compared between L. obcordata and L. bullata. Variability in storage behaviour between the three species was investigated through differential scanning calorimetry (DSC) by comparing thermal properties of lipids. L. obcordata seed were desiccation-tolerant and viability was retained when desiccated seed was stored for 24 months at 5 °C. L. bullata seed was both desiccation- and freezing-sensitive, while N. pedunculata was desiccation-sensitive. DSC analysis revealed that lipid crystallisation in L. bullata occurred between −18 °C and −49 °C and between −23 °C and −52 °C in L. obcordata and N. pedunculata. It is postulated that the metastable lipid phase, which coincides with the conventional seed banking temperature (i.e., storing seeds at −20 ± 4 °C and 15 ± 3% RH), could cause the seeds to age more rapidly through lipid peroxidation. Seeds of L. bullata, L. obcordata and N. pedunculata are best stored outside of their lipid metastable temperature ranges.
Identification and Characterization of Long Non-Coding RNAs: Implicating Insights into Their Regulatory Role in Kiwifruit Ripening and Softening during Low-Temperature Storage
Authors: Lai Ruilian , Wu Xiaopei , Feng Xin , Gao Minxia , Long Yu , Wu Rujian , Cheng Chunzhen , Chen Yiting
Published: March 2023

Long non-coding RNAs (lncRNAs) are crucial players regulating many biological processes in plants. However, limited knowledge is available regarding their roles in kiwifruit ripening and softening. In this study, using lncRNA-seq technology, 591 differentially expressed (DE) lncRNAs (DELs) and 3107 DE genes (DEGs) were identified from kiwifruit stored at 4 °C for 1, 2, and 3 weeks in comparison with non-treated control fruits. Of note, 645 DEGs were predicted to be targets of DELs (DEGTLs), including some DE protein-coding genes (such as β-amylase and pectinesterase). DEGTL-based GO enrichment analysis revealed that these genes were significantly enriched in cell wall modification and pectinesterase activity in 1 W vs. CK and 3 W vs. CK, which might be closely related to the fruit softening during low-temperature storage. Moreover, KEGG enrichment analysis revealed that DEGTLs were significantly associated with starch and sucrose metabolism. Our study revealed that lncRNAs play critical regulatory roles in kiwifruit ripening and softening under low-temperature storage, mainly by mediating the expression of starch and sucrose metabolism and cell wall modification related genes.
Identification of AREB/ABF Gene Family Involved in the Response of ABA under Salt and Drought Stresses in Jute (Corchorus olitorius L.)
Authors: Fiallos-Salguero Manuel Sebastian , Li Jing , Li Yunqing , Xu Jiantang , Fang Pingping , Wang Yankun , Zhang Liwu , Tao Aifen
Published: March 2023

The abscisic acid (ABA)-responsive element binding protein/ABRE-binding factor (AREB/ABF) subfamily members are essential to ABA signaling pathways and plant adaptation to various environmental stresses. Nevertheless, there are no reports on AREB/ABF in jute (Corchorus L.). Here, eight AREB/ABF genes were identified in the C. olitorius genome and classified into four groups (A–D) based on their phylogenetic relationships. A cis-elements analysis showed that CoABFs were widely involved in hormone response elements, followed by light and stress responses. Furthermore, the ABRE response element was involved in four CoABFs, playing an essential role in the ABA reaction. A genetic evolutionary analysis indicated that clear purification selection affects jute CoABFs and demonstrated that the divergence time was more ancient in cotton than in cacao. A quantitative real-time PCR revealed that the expression levels of CoABFs were upregulated and downregulated under ABA treatment, indicating that CoABF3 and CoABF7 are positively correlated with ABA concentration. Moreover, CoABF3 and CoABF7 were significantly upregulated in response to salt and drought stress, especially with the application of exogenous ABA, which showed higher intensities. These findings provide a complete analysis of the jute AREB/ABF gene family, which could be valuable for creating novel jute germplasms with a high resistance to abiotic stresses.
Soybean Seed Enrichment with Cobalt and Molybdenum as an Alternative to Conventional Seed Treatment
Authors: Abreu-Junior Cassio Hamilton , Gruberger Gabriel Asa Corrêa , Cardoso Paulo Henrique Silveira , Gonçalves Paula Wellen Barbosa , Nogueira Thiago Assis Rodrigues , Capra Gian Franco , Jani Arun Dilipkumar
Published: March 2023

Biological nitrogen fixation in soybean is enhanced when seed is treated with cobalt (Co) and molybdenum (Mo) prior to planting. In this study, our objective was to verify if Co and Mo application during the reproductive phase of the crop increases seed Co and Mo concentration without adverse effects on seed quality. Two experiments were conducted. First, we investigated foliar and soil Co and Mo application under greenhouse conditions. Next, we validated the results obtained in the first study. The treatments for both experiments consisted of Co doses combined with Mo, and a control without Co and Mo application. The foliar application was more efficient in producing enriched Co and Mo seed; meanwhile, as Co doses increased so did Co and Mo concentrations in the seed. There were no adverse effects on nutrition, development, quality, and yield of parent plants and seed when these micronutrients were applied. The seed showed higher germination, vigor, and uniformity for the development of soybean seedlings. We concluded that the application of 20 g ha−1 Co and 800 g ha−1 Mo via foliar application at the reproductive stage of soybean increased germination rate and achieved the best growth and vigor index of enriched seed.