bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose- and Sex-Dependent Bidirectional Relationship between Intravenous Fentanyl Self-Administration and Gut Microbiota
Authors: Ren Michelle , Lotfipour Shahrdad
Published: May 2022

Gut bacteria influence neural circuits in addiction-related behaviors. Given the association between opioid use, gastrointestinal distress, and microbial dysbiosis in humans and mice, we test the hypothesis that interactions between gut bacteria and the brain mediate the rewarding and reinforcing properties of fentanyl. We implant rats with intravenous catheters in preparation for fentanyl intravenous self-administration (IVSA) on an escalating schedule of reinforcement to determine factors that influence fentanyl intake, including sex, dose, and gut microbiota. Our data show the impact of fentanyl IVSA on gut microbiota diversity, as well as the role of gut microbiota on fentanyl IVSA, in Sprague Dawley rats in a sex- and dose-dependent manner (n = 10–16/group). We found that the diversity of gut microbiota within females dose-dependently predicts progressive but not fixed ratio schedules of fentanyl IVSA. Depending on sex and fentanyl dose, alpha diversity (richness and evenness measured with Shannon index) is either increased or decreased following fentanyl IVSA and predicts progressive ratio breakpoint. Our findings collectively suggest a role of gut bacteria in drug-related behavior, including motivation and reinforcement. This work provides feasibility for an intravenous fentanyl self-administration model and uncovers potential factors mediating drug use, which may lead to the development of effective addiction interventions.
Representative-Area Approach to Define Blast-Induced Ground Vibrations—Damage Prevention Criterion Abacus
Authors: Rodríguez Rafael , Bascompta Marc , Fernández Patricia , Fernández Pablo R.
Published: May 2022

Ground vibrations due to blasting can cause damage to nearby structures. In this context, a damage prevention criterion was developed to avoid this potential risk, establishing a limit value for the Peak Particle Velocity (PPV) as a function of ground natural frequency and type of structure to protect. In addition, several empirical attenuation laws to estimate the PPV and frequency as a function of the distance and amount of explosive were also developed. These models can be used to separately predict PPV and frequency, obtaining the representative point of the designed blast and decide if a potential damage could exist or not. The proposed approach allows one to simultaneously work with an attenuation law for the PPV and another one for the frequency, defining an area in the damage criterion abacus instead of a single representative point. The system was applied using data from 75 blasts in different limestone quarries in the north of Spain.
N-methyl Benzimidazole Tethered Cholic Acid Amphiphiles Can Eradicate S. aureus-Mediated Biofilms and Wound Infections
Authors: Kakkar Himanshu , Chaudhary Nalini , Mehta Devashish , Saini Varsha , Maheshwari Shallu , Singh Jitender , Walia Preeti , Bajaj Avinash
Published: May 2022

Infections associated with Gram-positive bacteria like S. aureus pose a major threat as these bacteria can develop resistance and thereby limit the applications of antibiotics. Therefore, there is a need for new antibacterials to mitigate these infections. Bacterial membranes present an attractive therapeutic target as these membranes are anionic in nature and have a low chance of developing modifications in their physicochemical features. Antimicrobial peptides (AMPs) can disrupt the microbial membranes via electrostatic interactions, but the poor stability of AMPs halts their clinical translation. Here, we present the synthesis of eight N-methyl benzimidazole substituted cholic acid amphiphiles as antibacterial agents. We screened these novel heterocyclic cholic acid amphiphiles against different pathogens. Among the series, CABI-6 outperformed the other amphiphiles in terms of bactericidal activity against S. aureus. The membrane disruptive property of CABI-6 using a fluorescence-based assay has also been investigated, and it was inferred that CABI-6 can enhance the production of reactive oxygen species. We further demonstrated that CABI-6 can clear the pre-formed biofilms and can mitigate wound infection in murine models.
Portable Digital Linear Ion Trap Mass Spectrometer Based on Separate-Region Corona Discharge Ionization Source for On-Site Rapid Detection of Illegal Drugs
Authors: Li Lingfeng , Zhang Tianyi , Wang Deting , Zhang Yunjing , He Xingli , Wang Xiaozhi , Li Peng
Published: May 2022

As narcotic control has become worse in the past decade and the death toll of drug abuse hits a record high, there is an increasing demand for on-site rapid detection of illegal drugs. This work developed a portable digital linear ion trap mass spectrometer based on separate-region corona discharge ionization source to meet this need. A separate design of discharge and reaction regions was adopted with filter air as both carrier gas for the analyte and protection of the corona discharge needle. The linear ion trap was driven by a digital waveform with a low voltage (±100 V) to cover a mass range of 50–500 Da with a unit resolution at a scan rate of 10,000 Da/s. Eighteen representative drugs were analyzed, demonstrating excellent qualitative analysis capability. Tandem mass spectrometry (MS/MS) was also performed by ion isolation and collision-induced dissociation (CID) with air as a buffer gas. With cocaine as an example, over two orders of magnitude dynamic range and 10 pg of detection limit were achieved. A single analysis time of less than 10 s was obtained by comparing the information of characteristic ions and product ions with the built-in database. Analysis of a real-world sample further validated the feasibility of the instrument, with the results benchmarked by GC-MS. The developed system has powerful analytical capability without using consumables including solvent and inert gas, meeting the requirements of on-site rapid detection applications.
Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems
Authors: Petrenko Daria , Chubarev Vladimir , Syzrantsev Nikita , Ismail Nafeeza , Merkulov Vadim , Sologova Susanna , Grigorevskikh Ekaterina , Smolyarchuk Elena , Alyautdin Renad
Published: May 2022

The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.
Individualized Dosage of Tacrolimus for Renal Transplantation Patients Based on Pharmacometabonomics
Authors: He Xiaoying , Yang Xi , Yan Xiaoting , Huang Mingzhu , Xiang Zheng , Lou Yan
Published: May 2022

The clinical pharmacodynamics of tacrolimus in renal transplant patients has significant interindividual variability. T lymphocytes were selected to study the pharmacodynamic response of tacrolimus, which was significantly correlated with renal function and the outcome of renal transplant patients. Ultra-performance liquid chromatography–quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) was performed to obtain the metabolic profiles of 109 renal transplant patients. A partial least squares (PLS) model was constructed to screen potential biomarkers that could predict the efficacy of tacrolimus. Multinomial logistic regression analysis established a bridge that could quantify the relationship between the efficacy of tacrolimus and biomarkers. The results showed a good correlation between endogenous molecules and the efficacy of tacrolimus. Metabolites such as serum creatinine, mesobilirubinogen, L-isoleucine, 5-methoxyindoleacetate, eicosapentaenoic acid, N2-succinoylarginine, tryptophyl-arginine, and butyric acid were indicated as candidate biomarkers. In addition, the key biomarkers could correctly predict the efficacy of tacrolimus with an accuracy of 82.5%. Finally, we explored the mechanism of individual variation by pathway analysis, which showed that amino acid metabolism was significantly related to the efficacy of tacrolimus. Moreover, orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there was no difference in key metabolites among different pharmacodynamic groups at 1 month and 3 months after dose adjustment, suggesting that pharmacometabonomics is a useful tool to predict individual differences in pharmacodynamics and thus to facilitate individualized drug therapy.
Antiproliferative and Proapoptotic Effects of Phenanthrene Derivatives Isolated from Bletilla striata on A549 Lung Cancer Cells
Authors: Zhou Fei , Feng Rui , Dai Ou , Yang Lian , Liu Yu , Tian Yun-Cai , Peng Cheng , Xiong Liang
Published: May 2022

Lung cancer continues to be the world’s leading cause of cancer death and the treatment of non-small cell lung cancer (NSCLC) has attracted much attention. The tubers of Bletilla striata are regarded as “an excellent medicine for lung diseases” and as the first choice to treat several lung diseases. In this study, seventeen phenanthrene derivatives, including two new compounds (1 and 2), were isolated from the tubers of B. striata. Most compounds showed cytotoxicity against A549 cells. An EdU proliferation assay, a cell cycle assay, a wound healing assay, a transwell migration assay, a flow cytometry assay, and a western blot assay were performed to further investigate the effect of compound 1 on A549 cells. The results showed that compound 1 inhibited cell proliferation and migration and promoted cell apoptosis in A549 cells. The mechanisms might correlate with the regulation of the Akt, MEK/ERK, and Bcl-2/Bax signaling pathways. These results suggested that the phenanthrenes of B. striata might be important and effective substances in the treatment of NSCLC.
Synthesis of Holmium-Oxide Nanoparticles for Near-Infrared Imaging and Dye-Photodegradation
Authors: Zhu Jia , Shao Xue-Jun , Li Zongan , Lin Chia-Hui , Wang Cheng-Wan-Qian , Jiao Keran , Xu Jian , Pan Hong-Xia , Wu Ye
Published: May 2022

The development of multifunctional nanomaterials has received growing research interest, thanks to its ability to combine multiple properties for severing highly demanding purposes. In this work, holmium oxide nanoparticles are synthesized and characterized by various tools including XRD, XPS, and TEM. These nanoparticles are found to emit near-infrared fluorescence (800–1100 nm) under a 785 nm excitation source. Imaging of the animal tissues was demonstrated, and the maximum imaging depth was found to be 2.2 cm. The synthesized nanoparticles also show the capability of facilitating dye (fluorescein sodium salt and rhodamine 6G) degradation under white light irradiation. The synthesized holmium oxide nanoparticles are envisioned to be useful for near-infrared tissue imaging and dye-degradation.
Synthesis, Characterization and Antimicrobial Activity of Zinc Oxide Nanoparticles against Selected Waterborne Bacterial and Yeast Pathogens
Authors: Klink Michael John , Laloo Neelan , Leudjo Taka Anny , Pakade Vusumzi Emmanuel , Monapathi Mzimkhulu Ephraim , Modise Johannes Sekomeng
Published: May 2022

The disinfection of wastewater using nanoparticles (NPs) has become a focal area of research in water treatment. In this study, zinc oxide (ZnO) NPs were synthesized using the microwave heating crystallization technique and characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Qualitative well diffusion and quantitative minimum inhibitory concentration (MIC) tests were conducted to determine the antimicrobial activity of ZnO NPs against selected waterborne pathogenic microbes. FTIR spectral studies confirmed that the binding of urea with Zn occurs through Zn–O stretching. XRD confirmed the crystallized identity in a hexagonal ZnO wurtzite-type structure. The formation of zones of inhibition and low MIC values in the antimicrobial analysis were indicative of the effective antimicrobial activity of zinc oxide nanoparticles against the test microorganisms. The application of metallic nanoparticles in water treatment could curb the spread of waterborne microbial diseases.
Jatrolignans C and D: New Neolignan Epimers from Jatropha curcas
Authors: He Yi-Lin , Huang Pei-Zhi , Yang Hong-Ying , Feng Wei-Jiao , Li Zhao-Cai , Gao Kun
Published: May 2022

Two new neolignans jatrolignans, C (1) and D (2), a pair of epimers, were isolated from the whole plants of Jatropha curcas L. (Euphorbiaceae). Their structures were determined with HRESIMS, IR, and NMR data analysis, and electronic circular dichroism (ECD) experiments via a comparison of the experimental and the calculated ECD spectra. Their antichlamydial activity was evaluated in Chlamydia abortus. They both showed dose-dependent antichlamydial effects. Significant growth inhibitory effects were observed at a minimum concentration of 40 μM.
Effect-Directed Profiling of Monofloral Honeys from Ethiopia by High-Performance Thin-Layer Chromatography and High-Resolution Mass Spectrometry
Authors: Morlock Gertrud E. , Belay Abera , Heil Julia , Mehl Annabel , Borck Hannelore
Published: May 2022

Ethiopian honey is used not only as food but also for treatment in traditional medicine. For its valorization, bioactive compounds were analyzed in nine types of monofloral Ethiopian honey. Therefore, a non-target effect-directed profiling was developed via high-performance thin-layer chromatography combined with multi-imaging and planar effect-directed assays. Characteristic bioactivity profiles of the different honeys were determined in terms of antibacterial, free-radical scavenging, and various enzyme inhibitory activities. Honeys from Hypoestes spp. and Leucas abyssinica showed low activity in all assays. In contrast, others from Acacia spp., Becium grandiflorum, Croton macrostachyus, Eucalyptus globulus, Schefflera abyssinica, Vernonia amygdalina, and Coffea arabica showed more intense activity profiles, but these differed depending on the assay. In particular, the radical scavenging activity of Croton macrostachyus and Coffea arabica honeys, the acetylcholinesterase-inhibiting activity of Eucalyptus globulus and Coffea arabica honeys, and the antibacterial activity of Schefflera abyssinica honey are highlighted. Bioactive compounds of interest were further characterized by high-resolution mass spectrometry. Identifying differences in bioactivity between mono-floral honey types affects quality designation and branding. Effect-directed profiling provides new insights that are valuable for food science and nutrition as well as for the market, and contributes to honey differentiation, categorization, and authentication.
Bicyclic Isoxazoline Derivatives: Synthesis and Evaluation of Biological Activity
Authors: Sedenkova Kseniya N. , Andriasov Kristian S. , Eremenko Marina G. , Grishin Yuri K. , Alferova Vera A. , Baranova Anna A. , Zefirov Nikolay A. , Zefirova Olga N. , Zarubaev Vladimir V. , Gracheva Yulia A. , Milaeva Elena R. , Averina Elena B.
Published: May 2022

The application of non-planar scaffolds in drug design allows for the enlargement of the chemical space, and for the construction of molecules that have more effective target–ligand interactions or are less prone to the development of resistance. Among the works of the last decade, a literature search revealed spirothiazamenthane, which has served as a lead in the development of derivatives active against resistant viral strains. In this work, we studied the novel molecular scaffold, which resembles spirothiazamenthane, but combines isoxazoline as a heterocycle and cyclooctane ring as a hydrophobic part of the structure. The synthesis of new 3-nitro- and 3-aminoisoxazolines containing spiro-fused or 1,2-annelated cyclooctane fragments was achieved by employing 1,3-dipolar cycloaddition of 3-nitro-4,5-dihydroisoxazol-4-ol 2-oxide or tetranitromethane-derived alkyl nitronates with non-activated alkenes. A series of spiro-sulfonamides was obtained by the reaction of 3-aminoisoxazoline containing a spiro-fused cyclooctane residue with sulfonyl chlorides. Preliminary screening of the compounds for antiviral, antibacterial, antifungal and antiproliferative properties in vitro revealed 1-oxa-2-azaspiro[4.7]dodec-2-en-3-amine and 3a,4,5,6,7,8,9,9a-octahydrocycloocta[d]isoxazol-3-amine with activity against the influenza A/Puerto Rico/8/34 (H1N1) virus in the submicromolar range, and high values of selectivity index. Further study of the mechanism of the antiviral action of these compounds, and the synthesis of their analogues, is likely to identify new agents against resistant viral strains.
Nanoparticles to Enhance Melting Performance of Phase Change Materials for Thermal Energy Storage
Authors: Han Yu , Yang Yan , Mallick Tapas , Wen Chuang
Published: May 2022

The present study proposes the phase change material (PCM) as a thermal energy storage unit to ensure the stability and flexibility of solar-energy-based heating and cooling systems. A mathematical model is developed to evaluate the PCM melting process, considering the effect of nanoparticles on heat transfer. We evaluate the role of nanoparticles (Al2O3-, copper- and graphene-based nanofluids) in enhancing the performance of the melting process of phase change materials. The results show that natural convection due to the buoyancy effect dominates the flow behaviour even in the initial stage of the PCM melting process. High natural convection at the bottom of the annular tube moves the melted PCM upward from the lateral, which pushes the liquid–solid interface downward. The addition of 3% vol Al2O3 nanoparticles boosts PCM melting performance by decreasing the melting time of PCM by approximately 15%. The comparison of Al2O3, copper and graphene nanoparticles demonstrates that higher thermal conductivity, ranging from 36 to 5000 W m−1 K−1, does not contribute to a significant improvement in the melting performance of PCMs.
Bactericidal and Antiviral Bionic Metalized Nanocoatings
Authors: Kryuchkov Mikhail , Adamcik Jozef , Katanaev Vladimir L.
Published: May 2022

In diverse living organisms, bionanocoatings provide multiple functionalities, to the surfaces they cover. We have, previously, identified the molecular mechanisms of Turing-based self-assembly of insect corneal nanocoatings and developed forward-engineering approaches to construct multifunctional soft bionic nanocoatings, encompassing the Drosophila protein Retinin. Here, we expand the versatility of the bionic nanocoatings, by identifying and using diverse Retinin-like proteins and different methods of their metallization, using nickel, silver, and copper ions. Comparative assessment, of the resulting bactericidal, antiviral, and cytotoxic properties, identifies the best protocols, to construct safe and anti-infective metalized bionic nanocoatings. Upscaled application of these protocols, to various public surfaces, may represent a safe and economic approach to limit hazardous infections.
Assisted Synthesis of Coated Iron Oxide Nanoparticles for Magnetic Hyperthermia
Authors: Ferreira Liliana P. , Reis César P. , Robalo Tiago T. , Melo Jorge M. E. , Ferreira Paula , Gonçalves Joana , Hajalilou Abdollah , Cruz Maria Margarida
Published: May 2022

Magnetite nanoparticles were synthesized by the co-precipitation method with and without the assistance of an additive, namely, gelatin, agar-agar or pectin, using eco-friendly conditions and materials embodying a green synthesis process. X-ray diffraction and transmission electron microscopy were used to analyze the structure and morphology of the nanoparticles. Magnetic properties were investigated by SQUID magnetometry and 57Fe Mössbauer spectroscopy. The results show that the presence of the additives implies a higher reproducibility of the morphological magnetic nanoparticle characteristics compared with synthesis without any additive, with small differences associated with different additives. To assess their potential for magnetic hyperthermia, water-based suspensions of these nanoparticles were prepared with and without citric acid. The stable solutions obtained were studied for their structural, magnetic and heating efficiency properties. The results indicate that the best additive for the stabilization of a water-based emulsion and better heating efficiency is pectin or a combination of pectin and agar-agar, attaining an intrinsic loss power of 3.6 nWg−1.
Efficacy and Safety of Nutrient Supplements for Glycaemic Control and Insulin Resistance in Type 2 Diabetes: An Umbrella Review and Hierarchical Evidence Synthesis
Authors: Fong Charmie , Alesi Simon , Mousa Aya , Moran Lisa J. , Deed Gary , Grant Suzanne , Tapia Kriscia , Ee Carolyn
Published: May 2022

Background: Nutrient supplements are widely used for type 2 diabetes (T2D), yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses, and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycaemic control, measures of insulin sensitivity and secretion), adverse events, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments. Quality was assessed using A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2). Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C, and omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) were superior to placebo for the primary outcome of glycated hemoglobin (HbA1c) (Mean Difference/MD −0.54, −0.54 and ES −0.27, respectively). Probiotics were superior to placebo for HbA1c (Weighted Mean Difference/WMD −0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD −0.17%). Magnesium, zinc, Vitamin C, probiotics, and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.
Relationship between Nutritional Status, Body Composition, Muscle Strength, and Functional Recovery in Patients with Proximal Femur Fracture
Authors: Irisawa Hiroshi , Mizushima Takashi
Published: May 2022

Sarcopenia is a major issue among the elderly. However, the effects of nutritional status and body composition on functional recovery in patients with proximal femur fractures (PFF) remain unclear. Hence, this study aimed to investigate the effects of nutritional status, body composition (skeletal muscle mass and muscle quality measured by phase angle [PhA] values), and muscle strength on the improvement in activities of daily living (ADL) in patients with PFF. We enrolled patients with PFF admitted to a rehabilitation unit. Nutritional status, body composition, grip strength, and motor Functional Independence Measure (FIM) score were assessed on admission day and at 4 weeks thereafter. Of 148 patients, 84 had femoral neck fractures, and 64 had trochanteric fractures. The mean motor FIM score was 49.2 points at admission and 64.9 points after 4 weeks. In multivariate analysis, higher geriatric nutritional risk index and PhA measured by anthropometry were associated with a significantly higher FIM score after 4 weeks. Muscle strength and quality changes significantly correlated with ADL improvement. Poor nutritional status and decreased muscle strength and quality interfered with ADL recovery. Nutritional management before injury and from the acute phase, and rehabilitation to maintain skeletal muscle status, are important for ADL recovery.
Association of Serum 25(OH)D with Metabolic Syndrome in Chinese Women of Childbearing Age
Authors: Shan Xiaoyun , Zhao Xiayu , Li Siran , Song Pengkun , Man Qingqing , Liu Zhen , Hu Yichun , Yang Lichen
Published: May 2022

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China. Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders. Results: Body mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS’s components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980–2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (<14.22 ng/mL) was significantly related to the risk of elevated waist circumference (WC) (OR = 1.612 (1.014–2.561)) and TG (OR = 2.210 (1.318–3.706)), and reduced HDL-C (OR = 1.639 (1.206–2.229)) after adjusting for the confounders among these women. Moreover, these relationships were not affected by vitamin D metabolism-related gene polymorphisms. Conclusion: After comprehensively considering various influencing factors, significant associations between insufficient serum 25(OH)D and MetS‘s components, including elevated WC, TG, and reduced HDL-C, were observed. However, MetS, hypertension, and hyperglycemia were not found independently associated with 25(OH)D levels.
Cornus mas L. Increases Glucose Uptake and the Expression of PPARG in Insulin-Resistant Adipocytes
Authors: Małodobra-Mazur Małgorzata , Cierzniak Aneta , Ryba Martyna , Sozański Tomasz , Piórecki Narcyz , Kucharska Alicja Z.
Published: May 2022

Cornus mas L., also known as cornelian cherry (CM), is a species that has long been cultivated in many different countries. In numerous scientific reports, cornelian cherry is used to treat numerous diseases and conditions. The presented study evaluated the effect of red and yellow Cornus mas L. extract on insulin sensitivity in adipocytes. 3T3-L1 fibroblasts as well as human SAT-derived and VAT-derived adipocytes were differentiated in vitro, and insulin resistance was induced using palmitic acid (16:0). The effect of CM fruit extract was analyzed in terms of glucose uptake and insulin signaling gene expression. In the glucose uptake test after insulin stimulation, a significant increase in glucose uptake was demonstrated in cells treated with CM fruit extracts. Furthermore, CM fruit extracts increased the expression of insulin signaling genes in adipocytes stimulated with insulin in control cells and adipocytes treated with CM extract. Additionally, a significant increase in peroxisome proliferator activated receptor gamma (PPARG) expression was observed in cells supplemented with CM extract. In conclusion, studies have shown that CM fruits can overcome insulin resistance and thus they have a positive effect on cell metabolism.
Habitual Total Drinking Fluid Intake Did Not Affect Plasma Hydration Biomarkers among Young Male Athletes in Beijing, China: A Cross-Sectional Study
Authors: Zhang Jianfen , Zhang Na , Li Yibin , He Hairong , Ma Guansheng
Published: May 2022

The purposes of this study were to explore the drinking patterns, and urinary and plasma hydration biomarkers of young adults with different levels of habitual total drinking fluid intake. A cross-sectional study was conducted among 111 young male athletes in Beijing, China. Total drinking fluids and water from food were assessed by a 7-day, 24-h fluid intake questionnaire and the duplicate portion method, respectively. The osmolality and electrolyte concentrations of the 24-h urine and fasting blood samples were tested. Differences in groups LD1 (low drinker), LD2, HD1, and HD2 (high drinker), divided according to the quartiles of total drinking fluids, were compared using one-way ANOVA, Kruskal–Wallis H-tests, and chi-squared tests. A total of 109 subjects completed the study. The HD2 group had greater amounts of TWI (total water intake) and higher and lower contributions of total drinking fluids and water from food to TWI, respectively, than the LD1, LD2, and HD1 groups (p < 0.05), but the amounts of water from food did not differ significantly among the four groups (all p > 0.05). Participants in the HD2 group had higher amounts of water than participants in the LD1, LD2, and HD1 groups (p < 0.05); SSBs were the second top contributor of total drinking fluids, ranging from 24.0% to 31.8%. The percentage of subjects in optimal hydration status increased from 11.8% in the LD1 group to 58.8% in the HD2 group (p < 0.05). The HD2 and HD1 groups had 212–227 higher volumes of urine than the LD1 and LD2 groups (p < 0.05). No significant differences were found in the plasma biomarkers (p > 0.05), with the exception of higher concentrations of K in the HD1 group than in the LD1 group (p < 0.05). Subjects with higher amounts of total drinking fluids had better hydration status than those with lower total drinking fluids, but not better drinking patterns. Habitual total drinking fluids did not affect the plasma biomarkers.
Association of Maternal Erythrocyte PUFA during Pregnancy with Offspring Allergy in the Chinese Population
Authors: Peng Shanshan , Du Zhicheng , He Yannan , Zhao Feng , Chen Yujing , Wu Shengchi , Hao Yuantao , Cai Li
Published: May 2022

Findings on prenatal polyunsaturated fatty acids (PUFA) and offspring allergies have been inconsistent, and the majority of studies have focused on Western populations. This study aimed to investigate the associations between maternal erythrocyte PUFA and offspring allergies in the first 2 years in the Chinese population. We included 573 mother–infant pairs from a birth cohort. Based on the outpatient medical records, we identified the diagnosis and time of offspring allergic disease onset. We measured erythrocyte fatty acids by gas chromatography. Associations were examined using Cox regression. We found that higher maternal total PUFA levels (HR = 0.80; 95% CI: 0.68, 0.94), especially of arachidonic acid (AA) (HR = 0.79; 95% CI: 0.65, 0.97) and n-3 PUFA (HR = 0.77; 95% CI: 0.62, 0.97), were associated with reduced risk of offspring allergies. Similar results were found for eczema. Compared with children without a maternal allergy history, the associations of total PUFA (p = 0.028) and n-6 PUFA (p = 0.013) with offspring allergies were stronger in those with a maternal allergy history. Maternal erythrocyte total PUFA, especially AA, and n-3 PUFA were inversely associated with offspring allergies within 2 years of age. There was a significant interaction between maternal allergy history and maternal PUFA in offspring allergies.
Exorbitant Drug Loading of Metformin and Sitagliptin in Mucoadhesive Buccal Tablet: In Vitro and In Vivo Characterization in Healthy Volunteers
Authors: Shakir Rouheena , Hanif Sana , Salawi Ahmad , Arshad Rabia , Sarfraz Rai , Irfan Muhammad , Raza Syed , Barkat Kashif , Sabei Fahad , Almoshari Yosif , Alshamrani Meshal , Syed Muhammad
Published: May 2022

The aim of the proposed study is to develop a mucoadhesive buccal delivery system for the sustained delivery of metformin (MET) and sitagliptin (SIT) against diabetes mellitus (DM) with improved bioavailability. Polymeric blend of Carbopol® 940 (CP), agarose (AG) or polyvinylpyrrolidone K30 (PVP) as mucoadhesive agents in formulations (R1–R15) were compressed via the direct compression technique. Tablets were characterized for solid state studies, physicochemical and in vivo mucoadhesion studies in healthy volunteers. Outcomes did not reveal any unusual peak or interaction between the drugs and polymers in the physical mixture through Fourier Transform Infrared Spectroscopy (FTIR) and DSC analysis. The mucoadhesive blend of CP and PVP was superior compared to other blends. The formulation R4 revealed exorbitant loading of drugs with complete drug release for 6 h with ex vivo mucoadhesive strength and time of 26.99 g and 8.1 h, respectively. It was further scrutinized to evaluate it as an optimized formulation where it was found to be stable for up to 6 months. The formulation R4 depicted Korsmeyer–Peppas model and first-order mode of release correspondingly for SIT and MET. Moreover, it showed hemocompatibility, biocompatibility and stability with non-significant changes in the dissolution profile. Overall, the CP blend with PVP was found appropriate to yield the desired release coupled with the optimized mucoadhesive properties of the buccal tablets, ensuring sufficient pharmaceutical stability.
Design, Synthesis, and In Vitro Evaluation of Novel 8-Amino-Quinoline Combined with Natural Antioxidant Acids
Authors: Bacci Andrea , Corsi Francesca , Runfola Massimiliano , Sestito Simona , Piano Ilaria , Manera Clementina , Saccomanni Giuseppe , Gargini Claudia , Rapposelli Simona
Published: May 2022

Overproduction of reactive oxygen species (ROS) and alterations in metallostasis are common and related hallmarks in several neurodegenerative diseases (NDDs). Nature-based derivatives always represent an attractive tool in MTDL drug design, especially against ROS in NDDs. On this notion, we designed a new series of 8-quinoline-N-substituted derivatives with a natural antioxidant portion (i.e., lipoic, caffeic, and ferulic acids). These compounds were shown to chelate copper, a metal involved in ROS-induced degeneration, and scavenger oxygen radicals in DPPH assay. Then, selected compounds 4 and 5 were evaluated in an in vitro model of oxidative stress and shown to possess cytoprotective effects in 661W photoreceptor-like cells. The obtained results may represent a starting point for the application of the proposed class of compounds in retinal neurodegenerative diseases such as retinitis pigmentosa (RP), comprising a group of hereditary rod–cone dystrophies that represent a major cause of blindness in patients of working age, where the progression of the disease is a multifactorial event, with oxidative stress contributing predominantly.
Application of a Physiologically Based Pharmacokinetic Model to Predict Cefazolin and Cefuroxime Disposition in Obese Pregnant Women Undergoing Caesarean Section
Authors: Alrammaal Hanadi H. , Abduljalil Khaled , Hodgetts Morton Victoria , Morris R. Katie , Marriott John F. , Chong Hsu P. , Batchelor Hannah K.
Published: May 2022

Intravenous (IV) cefuroxime and cefazolin are used prophylactically in caesarean sections (CS). Currently, there are concerns regarding sub-optimal dosing in obese pregnant women compared to lean pregnant women prior to CS. The current study used a physiologically based pharmacokinetic (PBPK) approach to predict cefazolin and cefuroxime pharmacokinetics in obese pregnant women at the time of CS as well as the duration that these drug concentrations remain above a target concentration (2, 4 or 8 µg/mL or µg/g) in plasma or adipose tissue. Cefazolin and cefuroxime PBPK models were first built using clinical data in lean and in obese non–pregnant populations. Models were then used to predict cefazolin and cefuroxime pharmacokinetics data in lean and obese pregnant populations. Both cefazolin and cefuroxime models sufficiently described their total and free levels in the plasma and in the adipose interstitial fluid (ISF) in non–pregnant and pregnant populations. The obese pregnant cefazolin model predicted adipose exposure adequately at different reference time points and indicated that an IV dose of 2000 mg can maintain unbound plasma and adipose ISF concentration above 8 µg/mL for 3.5 h post dose. Predictions indicated that an IV 1500 mg cefuroxime dose can achieve unbound plasma and unbound ISF cefuroxime concentration of ≥8 µg/mL up to 2 h post dose in obese pregnant women. Re-dosing should be considered if CS was not completed within 2 h post cefuroxime administration for both lean or obese pregnant if cefuroxime concentrations of ≥8 µg/mL is required. A clinical study to measure cefuroxime adipose concentration in pregnant and obese pregnant women is warranted.
Drug-Release Mechanisms Elucidated by Imaging Techniques: Visualizing the Invisible!
Authors: Florin-Muschert Susanne
Published: May 2022

Imaging techniques such as Raman spectroscopy, electron microscopy, laser scanning confocal microscopy, atomic force microscopy, tomography, magnetic resonance imaging, and terahertz are powerful tools to elucidate drug-release mechanisms from different types of delivery devices [...]
Progress in Gelatin as Biomaterial for Tissue Engineering
Authors: Lukin Izeia , Erezuma Itsasne , Maeso Lidia , Zarate Jon , Desimone Martin Federico , Al-Tel Taleb H. , Dolatshahi-Pirouz Alireza , Orive Gorka
Published: May 2022

Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a widely employed biomaterial in the field of tissue engineering: gelatin. Emerging techniques including 3D bioprinting and gelatin functionalization have demonstrated better mimicking of native tissue by reinforcing gelatin-based systems, among others. This breakthrough facilitates, on the one hand, the manufacturing process when it comes to practicality and cost-effectiveness, which plays a key role in the transition towards clinical application. On the other hand, it can be concluded that gelatin could be considered as one of the promising biomaterials in future trends, in which the focus might be on the detection and diagnosis of diseases rather than treatment.
Utility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin
Authors: DuBois Megan , Tseng Angela , Francis Sunday M. , Haynos Ann F. , Peterson Carol B. , Jacob Suma
Published: May 2022

Oxytocin (OT), a mammalian neurohormone associated with social cognition and behavior, can be administered in its synthetic form intranasally (IN) and impact brain chemistry and behavior. IN-OT shows potential as a noninvasive intervention for disorders characterized by social challenges, e.g., autism spectrum disorder (ASD) and anorexia nervosa (AN). To evaluate IN-OT’s efficacy, we must quantify OT uptake, availability, and clearance; thus, we assessed OT levels in urine (uOT) before and after participants (26 ASD, 7 AN, and 7 healthy controls) received 40 IU IN-OT or placebo across two sessions using double-blind, placebo-controlled crossover designs. We also measured uOT and plasma (pOT) levels in a subset of participants to compare the two sampling methods. We found significantly higher uOT and pOT following intranasal delivery of active compound versus placebo, but analyses yielded larger effect sizes and more clearly differentiated pre–post-OT levels for uOT than pOT. Further, we applied a two-step cluster (TSC), blinded backward-chaining approach to determine whether active/placebo groups could be identified by uOT and pOT change alone; uOT levels may serve as an accessible and accurate systemic biomarker for OT dose–response. Future studies will explore whether uOT levels correlate directly with behavioral targets to improve dosing for therapeutic goals.
Multi-Strain-Probiotic-Loaded Nanoparticles Reduced Colon Inflammation and Orchestrated the Expressions of Tight Junction, NLRP3 Inflammasome and Caspase-1 Genes in DSS-Induced Colitis Model
Authors: Alkushi Abdullah Glil , Elazab Sara T. , Abdelfattah-Hassan Ahmed , Mahfouz Hala , Salem Gamal A. , Sheraiba Nagwa I. , Mohamed Eman A. A. , Attia Mai S. , El-Shetry Eman S. , Saleh Ayman A. , ElSawy Naser A. , Ibrahim Doaa
Published: May 2022

Gut modulation by multi-strain probiotics (MSPs) is considered an effective strategy for treating inflammatory bowel disease (IBD). The combination of nanomaterial-based MSPs can improve their viability and resistance and can allow their targeted release in the gastrointestinal tract to be achieved. Thus, our aim is to investigate the prospective role of MSP integration into nanomaterials (MSPNPs) and the underlying molecular mechanisms supporting their application as an alternative therapy for IBD using a colitis rat model. To induce the colitis model, rats received 5% DSS, and the efficacy of disease progression after oral administration of MSPNPs was assessed by evaluating the severity of clinical signs, inflammatory response, expressions of tight-junction-related genes and NLRP3 inflammasome and caspase-1 genes, microbial composition and histopathological examination of colonic tissues. The oral administration of MSPNPs successfully alleviated the colonic damage induced by DSS as proved by the reduced severity of clinical signs and fecal calprotectin levels. Compared with the untreated DSS-induced control group, the high activities of colonic NO and MPO and serum CRP levels were prominently reduced in rats treated with MSPNPs. Of note, colonic inflammation in the group treated with MSPNPs was ameliorated by downstreaming NLRP3 inflammasome, caspase-1, IL-18 and IL-1β expressions. After colitis onset, treatment with MSPNPs was more effective than that with free MSPs in restoring the expressions of tight-junction-related genes (upregulation of occludin, ZO-1, JAM, MUC and FABP-2) and beneficial gut microbiota. Interestingly, treatment with MSPNPs accelerated the healing of intestinal epithelium as detected in histopathological findings. In conclusion, the incorporation of MPSs into nanomaterials is recommended as a perspective strategy to overcome the challenges they face and augment their therapeutic role for treating of colitis.
Implementing Brief Tobacco Cessation Interventions in Community Pharmacies: An Application of Rogers’ Diffusion of Innovations Theory
Authors: Hilts Katy Ellis , Corelli Robin L. , Prokhorov Alexander V. , Zbikowski Susan M. , Zillich Alan J. , Hudmon Karen Suchanek
Published: May 2022

Pharmacists, as highly accessible members of the healthcare team, have considerable potential to address tobacco use among patients. However, while published data suggest that pharmacists are effective in helping patients quit, barriers exist to routine implementation of cessation services in community pharmacy settings. Within the context of a randomized trial (n = 64 pharmacies), surveys were administered over a period of 6 months to assess pharmacists’ perceptions of factors associated with the implementation of “Ask-Advise-Refer”, a brief intervention approach that facilitates patient referrals to the tobacco quitline. Study measures, grounded in Rogers’ Diffusion of Innovations Theory, assessed pharmacists’ perceptions of implementation facilitators and barriers, perceptions of intervention materials provided, and perceived efforts and personal success in implementing Ask-Advise-Refer at 6-months follow-up. Findings indicate that while the brief intervention approach was not difficult to understand or implement, integration into normal workflows presents greater challenges and is associated with overall confidence and implementation success. Lack of time was the most significant barrier to routine implementation. Most (90.6%) believed that community pharmacies should be active in promoting tobacco quitlines. Study results can inform future development of systems-based approaches that lead to broad-scale adoption of brief interventions, including but not limited to tobacco cessation, in pharmacy settings.
Nonlinear Error Correction for Color Phase-Shifting Profilometry with Histogram Equalization
Authors: Cai Bolin , Zhu Haojie , Tong Chenen , Liu Lu
Published: May 2022

Because color patterns with multiple channels can carry more information than gray patterns with only one channel, color phase-shifting profilometry (CPSP) has been widely used for high-speed, three-dimensional (3D) shape measurement. However, the accuracy of CPSP suffers from nonlinear errors caused by color crosstalk. This paper presents an effective nonlinear error correction method for CPSP based on histogram equalization. The two main steps of the proposed method are eliminating nonlinear errors with histogram equalization and optimizing the results using a spline fitting algorithm. Compared with other compensation methods, the proposed approach does not require any precalibration information or additional patterns, which are very time-consuming. The simulations and experiments indicate that the proposed method has a promising performance for nonlinear error elimination.
Influence of Spatio-Temporal Couplings on Focused Optical Vortices
Authors: Talposi Anda-Maria , Iancu Vicentiu , Ursescu Daniel
Published: May 2022

Ultra-intense laser pulses with helical phases are of interest in laser-driven charged particle acceleration and related experiments with extreme light. However, such optical vortices can be affected by the presence of residual spatial-temporal couplings. Their field distributions after propagating in free-space and in the focal plane of an ideal focusing mirror were assessed through numerical modeling, based on the Gaussian decomposition method for a 25 fs pulse with a Supergaussian spatial profile. The wash-out of the central hole in the doughnut-shaped profile in the focal plane corresponds to the rotation of the phase discontinuity.