bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Exposure during the Active Phase Affects the Short-Chain Fatty Acid Production of Mice in a Time-Specific Manner
Authors: Ichikawa Natsumi , Sasaki Hiroyuki , Lyu Yijin , Furuhashi Shota , Watabe Aato , Imamura Momoko , Hayashi Katsuki , Shibata Shigenobu
Published: December 2021

Chronic or acute ambient temperature change alter the gut microbiota and the metabolites, regulating metabolic functions. Short-chain fatty acids (SCFAs) produced by gut bacteria reduce the risk of disease. Feeding patterns and gut microbiota that are involved in SCFAs production are controlled by the circadian clock. Hence, the effect of environmental temperature change on SCFAs production is expected depending on the exposure timing. In addition, there is limited research on effects of habitual cold exposure on the gut microbiota and SCFAs production compared to chronic or acute exposure. Therefore, the aim was to examine the effect of cold or heat exposure timing on SCFAs production. After exposing mice to 7 or 37 °C for 3 h a day at each point for 10 days, samples were collected, and cecal pH, SCFA concentration, and BAT weight was measured. As a result, cold exposure at ZT18 increased cecal pH and decreased SCFAs. Intestinal peristalsis was suppressed due to the cold exposure at ZT18. The results reveal differing effects of intermittent cold exposure on the gut environment depending on exposure timing. In particular, ZT18 (active phase) is the timing to be the most detrimental to the gut environment of mice.
Current Development in Interdigital Transducer (IDT) Surface Acoustic Wave Devices for Live Cell In Vitro Studies: A Review
Authors: Mazalan Mazlee , Noor Anas , Wahab Yufridin , Yahud Shuhaida , Zaman Wan
Published: December 2021

Acoustics have a wide range of uses, from noise-cancelling to ultrasonic imaging. There has been a surge in interest in developing acoustic-based approaches for biological and biomedical applications in the last decade. This review focused on the application of surface acoustic waves (SAW) based on interdigital transducers (IDT) for live-cell investigations, such as cell manipulation, cell separation, cell seeding, cell migration, cell characteristics, and cell behaviours. The approach is also known as acoustofluidic, because the SAW device is coupled with a microfluidic system that contains live cells. This article provides an overview of several forms of IDT of SAW devices on recently used cells. Conclusively, a brief viewpoint and overview of the future application of SAW techniques in live-cell investigations were presented.
Single-Wedge Lift-Out for Atom Probe Tomography Al/Ni Multilayers Specimen Preparation Based on Dual-Beam-FIB
Authors: Qiao Yi , Zhao Yalong , Zhang Zheng , Liu Binbin , Li Fusheng , Tong Huan , Wu Jintong , Zhou Zhanqi , Xu Zongwei , Zhang Yue
Published: December 2021

Atomic probe tomography (APT) samples with Al/Ni multilayer structure were successfully prepared by using a focused ion beam (FIB), combining with a field emission scanning electron microscope, with a new single-wedge lift-out method and a reduced amorphous damage layer of Ga ions implantation. The optimum vertex angle and preparation parameters of APT sample were discussed. The double interdiffusion relationship of the multilayer films was successfully observed by the local electrode APT, which laid a foundation for further study of the interface composition and crystal structure of the two-phase composites.
Structural Design and Optimization of a Resonant Micro-Accelerometer Based on Electrostatic Stiffness by an Improved Differential Evolution Algorithm
Authors: Huang Libin , Li Qike , Qin Yan , Ding Xukai , Zhang Meimei , Zhao Liye
Published: December 2021

This study designed an in-plane resonant micro-accelerometer based on electrostatic stiffness. The accelerometer adopts a one-piece proof mass structure; two double-folded beam resonators are symmetrically distributed inside the proof mass, and only one displacement is introduced under the action of acceleration, which reduces the influence of processing errors on the performance of the accelerometer. The two resonators form a differential structure that can diminish the impact of common-mode errors. This accelerometer realizes the separation of the introduction of electrostatic stiffness and the detection of resonant frequency, which is conducive to the decoupling of accelerometer signals. An improved differential evolution algorithm was developed to optimize the scale factor of the accelerometer. Through the final elimination principle, excellent individuals are preserved, and the most suitable parameters are allocated to the surviving individuals to stimulate the offspring to find the globally optimal ability. The algorithm not only maintains the global optimality but also reduces the computational complexity of the algorithm and deterministically realizes the optimization of the accelerometer scale factor. The electrostatic stiffness resonant micro-accelerometer was fabricated by deep dry silicon-on-glass (DDSOG) technology. The unloaded resonant frequency of the accelerometer resonant beam was between 24 and 26 kHz, and the scale factor of the packaged accelerometer was between 54 and 59 Hz/g. The average error between the optimization result and the actual scale factor was 7.03%. The experimental results verified the rationality of the structural design.
What Is the Role of Gut Microbiota in Obesity Prevalence? A Few Words about Gut Microbiota and Its Association with Obesity and Related Diseases
Authors: Tokarek Julita , Gadzinowska Joanna , Młynarska Ewelina , Franczyk Beata , Rysz Jacek
Published: December 2021

Obesity is becoming the most dangerous lifestyle disease of our time, and its effects are already being observed in both developed and developing countries. The aim of this study was to investigate the impact of gut microbiota on the prevalence of obesity and associated morbidities, taking into consideration underlying molecular mechanisms. In addition to exploring the relationship between obesity and fecal microorganisms with their metabolites, the study also focused on the factors that would be able to stimulate growth and remodeling of microbiota. Assessed articles were carefully classified according to a predetermined criterion and were critically appraised and used as a basis for conclusions. The considered articles and reviews acknowledge that intestinal microbiota forms a multifunctional system that might significantly affect human homeostasis. It has been proved that alterations in the gut microbiota are found in obese and metabolically diseased patients. The imbalance of microbiome composition, such as changes in Bacteroidetes/Firmicutes ratio and presence of different species of genus Lactobacillus, might promote obesity and comorbidities (type 2 diabetes mellitus, hypertension, dyslipidemia, depression, obstructive sleep apnea). However, there are also studies that contradict this theory. Therefore, further well-designed studies are needed to improve the knowledge about the influence of microbiota, its metabolites, and probiotics on obesity.
Microbial Steroid Production Technologies: Current Trends and Prospects
Authors: Donova Marina
Published: December 2021

This Special Issue aims to collect articles and reviews on new methodologies, research, and achievements in the field of steroid microbial biotechnologies [...]
Identification of the Bacterial Pathogens in Children with Otitis Media: A Study in the Northwestern Portuguese District of Braga
Authors: Silva Maria Daniela , Lima António , Marçal Nuno , Dias Luís , Gama Miguel , Sillankorva Sanna
Published: December 2021

Understanding the bacterial etiology of otitis media (OM) is important when designing and evaluating the best course of treatment. This study analyzed middle ear fluid (MEF) and nasopharynx (NP) samples collected from 49 children with OM undergoing myringotomy in the northwestern Portuguese district of Braga. A correlation between species in the NP and MEF was observed following pathogen detection by culture and quantitative polymerase chain reaction (qPCR) methods. Bacterial identification using culturing methods showed that Moraxella catarrhalis was the most representative in NP and MEF, followed by Streptococcus pneumoniae. However, qPCR of MEF showed a higher prevalence (61%) of Haemophilus influenzae. S. pneumoniae was not the most frequently identified species, but it still remains one of the leading causes of OM in this region despite 93.9% of the children being vaccinated with the pneumococcal conjugate vaccine. Furthermore, 46% of the samples analyzed by qPCR identified more than two bacterial species. M. catarrhalis and S. pneumoniae were the most frequent combination identified in NP and MEF samples by culturing methods. Additionally, a few NP and MEF samples simultaneously presented the three main otopathogens. These results point out that polymicrobial infections play an important role in OM. Further studies characterizing the serotypes of the strains isolated, their resistance profile, and their biofilm forming ability would help in the development of more targeted strategies against otitis media.
An Association of Pathogens and Biofilms with Alzheimer’s Disease
Authors: Chakravarthi Sandhya T. , Joshi Suresh G.
Published: December 2021

As one of the leading causes of dementia, Alzheimer’s disease (AD) is a condition in which individuals experience progressive cognitive decline. Although it is known that beta-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) of tau fibrils are hallmark characteristics of AD, the exact causes of these pathologies are still mostly unknown. Evidence that infectious diseases may cause AD pathology has been accumulating for decades. The association between microbial pathogens and AD is widely studied, and there are noticeable correlations between some bacterial species and AD pathologies, especially spirochetes and some of the oral microbes. Borrelia burgdorferi has been seen to correlate with Aβ plaques and NFTs in infected cells. Because of the evidence of spirochetes in AD patients, Treponema pallidum and other oral treponemes are speculated to be a potential cause of AD. T. pallidum has been seen to form aggregates in the brain when the disease disseminates to the brain that closely resemble the Aβ plaques of AD patients. This review examines the evidence as to whether pathogens could be the cause of AD and its pathology. It offers novel speculations that treponemes may be able to induce or correlate with Alzheimer’s disease.
Water Relations, Gas Exchange, Chlorophyll Fluorescence and Electrolyte Leakage of Ectomycorrhizal Pinus halepensis Seedlings in Response to Multi-Heavy Metal Stresses (Pb, Zn, Cd)
Authors: Hachani Chadlia , Lamhamedi Mohammed S. , Zine El Abidine Abdenbi , Abassi Mejda , Khasa Damase P. , Béjaoui Zoubeir
Published: December 2021

The success of mine site restoration programs in arid and semi-arid areas poses a significant challenge and requires the use of high-quality seedlings capable of tolerating heavy metal stresses. The effect of ectomycorrhizal fungi on different physiological traits was investigated in Pinus halepensis seedlings grown in soil contaminated with heavy metals (Pb-Zn-Cd). Ectomycorrhizal (M) and non-ectomycorrhizal (NM) seedlings were subjected to heavy metals stress (C: contaminated, NC: control or non-contaminated) soils conditions for 12 months. Gas exchange, chlorophyll fluorescence, water relations parameters derived from pressure–volume curves and electrolyte leakage were evaluated at 4, 8 and 12 months. Ectomycorrhizal symbiosis promoted stronger resistance to heavy metals and improved gas exchange parameters and water-use efficiency compared to the non-ectomycorrhizal seedlings. The decrease in leaf osmotic potentials (Ψπ100: osmotic potential at saturation and Ψπ0: osmotic potential with loss of turgor) was higher for M-C seedling than NM-C ones, indicating that the ectomycorrhizal symbiosis promotes cellular osmotic adjustment and protects leaf membrane cell against leakage induced by Pb, Zn and Cd. Our results suggest that the use of ectomycorrhizal symbiosis is among the promising practices to improve the morphophysiological quality of seedlings produced in forest nurseries, their performance and their tolerance to multi-heavy metal stresses.
Structural Variations across Wolframite Solid Solutions, (Fe,Mn)WO4
Authors: Umbsaar Darren A. , Antao Sytle M.
Published: December 2021

The crystal structure of four samples from natural wolframite solid solutions, (Fe,Mn)WO4, was obtained with synchrotron high-resolution powder X-ray diffraction (HRPXRD) data, Rietveld refinements, space group P2/c, and Z = 2. Wolframite solid solutions extend from ferberite (FeWO4) to hübnerite (MnWO4). The W and (Mn,Fe) cations are in six-fold coordination. This study shows that the unit-cell parameters, a, b, c, and β angle, vary linearly with the unit-cell volume, V, across the wolframite series. The average  distance increases linearly because of larger Mn2+ (0.83 Å) replacing smaller Fe2+ (0.78 Å) cations, whereas the average  distance increases slightly because of the higher effective charge of the smaller Fe2+ cation. The distortions of the two types of polyhedra across the series are discussed.
Human Biomonitoring of Selected Hazardous Compounds in Portugal: Part II—Lessons Learned on Mycotoxins
Authors: Pena Angelina , Duarte Sofia , Pereira André M. P. T. , Silva Liliana J. G. , Laranjeiro Célia S. M. , Oliveira Marta , Lino Celeste , Morais Simone
Published: December 2021

Human biomonitoring (HBM) data provide information on total exposure regardless of the route and sources of exposure. HBM studies have been applied to quantify human exposure to contaminants and environmental/occupational pollutants by means of determining the parent compounds, their metabolites, or even their reaction products in biological matrices. HBM studies performed among the Portuguese population are dispersed and limited. Thus, to overcome this knowledge gap, this work reviews the published Portuguese HBM information concerning mycotoxins detected in the urine, serum, milk, hair, and nails of different groups of the Portuguese population. This integrative approach to the available HBM data allows us to analyze the main determinants and patterns of exposure of the Portuguese population to the selected hazardous compounds, as well as to assess the potential health risks. We also aimed to identify the main difficulties and challenges of HBM through the analysis of the enrolled studies. Ultimately, this study aims to support national and European policies in promoting human health by summarizing the most important outcomes and lessons learned through the HBM studies carried out in Portugal.
Functional Analysis of Sterol O-Acyltransferase Involved in the Biosynthetic Pathway of Pachymic Acid in Wolfiporia cocos
Authors: Zhu Wenjun , Liu Ying , Tang Jing , Liu Heping , Jing Naliang , Li Fengfeng , Xu Ran , Shu Shaohua
Published: December 2021

Pachymic acid from Wolfiporia cocos possesses important medicinal values including anti-bacterial, anti-inflammatory, anti-viral, invigorating, anti-rejection, anti-tumor, and antioxidant activities. However, little is known about the biosynthetic pathway from lanostane to pachymic acid. In particular, the associated genes in the biosynthetic pathway have not been characterized, which limits the high-efficiency obtaining and application of pachymic acid. To characterize the synthetic pathway and genes involved in pachymic acid synthesis, in this study, we identified 11 triterpenoids in W. cocos using liquid chromatography tandem mass spectrometry (LC-MS/MS), and inferred the putative biosynthetic pathway from lanostane to pachymic acid based on analyzing the chemical structure of triterpenoids and the transcriptome data. In addition, we identified a key gene in the biosynthetic pathway encoding W. cocos sterol O-acyltransferase (WcSOAT), which catalyzes tumolusic acid to pachymic acid. The results show that silence of WcSOAT gene in W. cocos strain led to reduction of pachymic acid production, whereas overexpression of this gene increased pachymic acid production, indicating that WcSOAT is involved in pachymic acid synthesis in W. cocos and the biosynthesis of W. cocos pachymic acid is closely dependent on the expression of WcSOAT gene. In summary, the biosynthetic pathway of pachymic acid and the associated genes complement our knowledge on the biosynthesis of W. cocos pachymic acid and other triterpenoids, and also provides a reference for target genes modification for exploring high-efficiency obtaining of active components.
Macrophage-Mediated Immune Responses: From Fatty Acids to Oxylipins
Authors: Balestrieri Barbara , Di Costanzo David , Dwyer Daniel F.
Published: December 2021

Macrophages have diverse functions in the pathogenesis, resolution, and repair of inflammatory processes. Elegant studies have elucidated the metabolomic and transcriptomic profiles of activated macrophages. However, the versatility of macrophage responses in inflammation is likely due, at least in part, to their ability to rearrange their repertoire of bioactive lipids, including fatty acids and oxylipins. This review will describe the fatty acids and oxylipins generated by macrophages and their role in type 1 and type 2 immune responses. We will highlight lipidomic studies that have shaped the current understanding of the role of lipids in macrophage polarization.
Phytochemical Profile and Anticancer Potential of Endophytic Microorganisms from Liverwort Species, Marchantia polymorpha L.
Authors: Stelmasiewicz Mateusz , Świątek Łukasz , Ludwiczuk Agnieszka
Published: December 2021

Liverwort endophytes could be a source of new biologically active substances, especially when these spore-forming plants are known to produce compounds that are not found in other living organisms. Despite the significant development of plant endophytes research, there are only a few studies describing liverwort endophytic microorganisms and their metabolites. In the presented study, the analysis of the volatile compounds obtained from thallose liverwort species, Marchantia polymorpha L., and its endophytes was carried out. For this purpose, non-polar extracts of plant material and symbiotic microorganisms were obtained. The extracts were analyzed using gas chromatography coupled to mass spectrometry. Compounds with the structure of diketopiperazine in the endophyte extract were identified. Liverwort volatile extract was a rich source of cuparane-, chamigrane-, acorane-, and thujopsane-type sesquiterpenoids. The cytotoxicity of ethyl acetate extracts from endophytic microorganisms was evaluated on a panel of cancer (FaDu, HeLa, and SCC-25) cell lines and normal (VERO), and revealed significant anticancer potential towards hypopharyngeal squamous cell carcinoma and cervical adenocarcinoma.
Ring-Opening Polymerization of ε-Caprolactone and Styrene Oxide–CO2 Coupling Reactions Catalyzed by Chelated Dehydroacetic Acid–Imine Aluminum Complexes
Authors: Wang Ting-Yen , Su Yu-Chia , Ko Bao-Tsan , Hsu Yu , Zeng Yu-Fang , Hu Ching-Han , Datta Amitabha , Huang Jui-Hsien
Published: December 2021

A series of chelated dehydroacetic acid–imine-based ligands L1H~L4H was synthesized by reacting dehydroacetic acid with 2-t-butylaniline, (S)-1-phenyl-ethylamine, 4-methoxylbenzylamine, and 2-(aminoethyl)pyridine, respectively, in moderate yields. Ligands L1H~L4H reacted with AlMe3 in toluene to afford corresponding compounds AlMe2L1 (1), AlMe2L2 (2), AlMe2L3 (3), and AlMe2L4 (4). All the ligands and aluminum compounds were characterized by IR spectra, 1H and 13C NMR spectroscopy. Additionally, the ligands L1H~L4H and corresponding aluminum derivatives 1, 3, and 4 were characterized by single-crystal X-ray diffractometry. The catalytic activities using these aluminum compounds as catalysts for the ε-caprolactone ring-opening polymerization (ROP) and styrene oxide-CO2 coupling reactions were studied. The results show that increases in the reaction temperature and selective solvent intensify the conversions of ε-caprolactone to polycaprolactone. Regarding the coupling reactions of styrene oxide and CO2, the conversion rate is over 90% for a period of 12 h at 90 °C. This strategy dispenses the origination of cyclic styrene carbonates, which is an appealing concern because of the transformation of CO2 into an inexpensive, renewable and easy excess carbon feedstock.
Adolescent Self-Efficacy for Diet and Exercise Following a School-Based Multicomponent Lifestyle Intervention
Authors: Efthymiou Vasiliki , Charmandari Evangelia , Vlachakis Dimitrios , Tsitsika Artemis , Pałasz Artur , Chrousos George , Bacopoulou Flora
Published: December 2021

Self-efficacy is perhaps the most important parameter associated with behavioral changes. The main aim of this study was to provide insight into the diet and exercise self-efficacy of Greek adolescents and how they could be modified via a multilevel multicomponent school-based lifestyle intervention. Secondary aims were to study the associations of students’ dietary and exercise self-efficacy indices with their anthropometric and sociodemographic parameters. A representative sample of the adolescent population in Attica, consisting of 1610 adolescents aged 12–17 years, recruited from 23 public high schools in three municipalities of the Attica area in Greece, received a three-component lifestyle educational intervention for health promotion and underwent screening for characteristics of metabolic syndrome with the use of portable telemedicine. All assessments and anthropometric measurements were performed at baseline and after the 6-month intervention. Anthropometric measurements included body mass index, waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR). Assessment tools included the Self-efficacy for Diet and the Self-efficacy for Exercise questionnaires, as well as the Mediterranean Diet Quality Index in Children and Adolescents (KIDMED). Analysis included 1020 adolescent students (421 males and 599 females), who completed the self-efficacy questionnaires pre- and post-intervention. Overall, the dietary (p < 0.001) and exercise (p < 0.001) self-efficacy increased significantly post-intervention. Post-intervention, all adolescents decreased their abdominal obesity indices (WC, WHtR, WHR), and this improvement was even more pronounced and significant (p = 0.019, p = 0.019, p = 0.023 respectively) in the adolescents with overweight/obesity. Post-intervention, the proportion of adolescents with normal weight increased from 73.9% to 78.6%, whereas the proportion of adolescents with overweight and obesity decreased from 20.4% to 15.9% and from 5.7% to 5.5%, respectively. Abdominal obesity also decreased from 10.4% to 9.0%. Female adolescents achieved significantly (p = 0.010) higher changes in diet self-efficacy than males. Other sociodemographic characteristics such as family structure, parental age, parental educational level and family income showed non-significant differences. Adolescents with higher KIDMED scores manifested significantly higher dietary and exercise self-efficacy than those with lower KIDMED scores. Both adolescents with normal weight and overweight/obesity manifested a reciprocal relation between diet and exercise self-efficacy. Multicomponent lifestyle interventions in the school environment may provide a first step in students’ behavior changes and provide grounds for future prevention programs in youth.
Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants
Authors: Nishida Yasuhiro , Nawaz Allah , Hecht Karen , Tobe Kazuyuki
Published: December 2021

Astaxanthin is a member of the carotenoid family that is found abundantly in marine organisms, and has been gaining attention in recent years due to its varied biological/physiological activities. It has been reported that astaxanthin functions both as a pigment, and as an antioxidant with superior free radical quenching capacity. We recently reported that astaxanthin modulated mitochondrial functions by a novel mechanism independent of its antioxidant function. In this paper, we review astaxanthin’s well-known antioxidant activity, and expand on astaxanthin’s lesser-known molecular targets, and its role in mitochondrial energy metabolism.
Artichoke and Bergamot Phytosome Alliance: A Randomized Double Blind Clinical Trial in Mild Hypercholesterolemia
Authors: Riva Antonella , Petrangolini Giovanna , Allegrini Pietro , Perna Simone , Giacosa Attilio , Peroni Gabriella , Faliva Milena Anna , Naso Maurizio , Rondanelli Mariangela
Published: December 2021

Botanicals are natural alternatives to pharmacological therapies that aim at reducing hypercholesterolemia. In this context, despite bergamot being effective in modulating lipid profile, some subjects failed to achieve a satisfactory response to supplementation. The aim of this study was to evaluate whether the association of 600 mg of bergamot phytosome® (from Citrus Bergamia Risso) and 100 mg of artichoke leaf standardized dry extract (from Cynara cardunculus L.) can be an alternative in patients with mild hypercholesterolemia who are poor responders to bergamot in a 2-month randomized placebo-controlled trial. Sixty overweight adults were randomized into two groups: 30 were supplemented and 30 received a placebo. The metabolic parameters and DXA body composition were evaluated at the start, after 30 and 60 days. Between the two groups, total and LDL cholesterol in the supplemented group (compared to placebo) showed significant decreases overtime. A significant reduction of waist circumference and visceral adipose tissue (VAT) was recorded in the supplemented group (compared to placebo), even in subjects who did not follow a low-calorie diet. In conclusion, the synergism between Citrus Bergamia polyphenols and Cynara cardunculus extracts may be an effective option and may potentially broaden the therapeutic role of botanicals in dyslipidemic patients.
Synthesis, Stability, and Bioavailability of Nicotinamide Riboside Trioleate Chloride
Authors: Zarei Amin , Khazdooz Leila , Madarshahian Sara , Enayati Mojtaba , Mosleh Imann , Lin Tiantian , Yan Bing , Ufheil Gerhard , Wooster Timothy James , Abbaspourrad Alireza
Published: December 2021

Nicotinamide riboside chloride (NRCl) is an effective form of vitamin B3. However, it cannot be used in ready-to-drink (RTD) beverages or high-water activity foods because of its intrinsic instability in water. To address this issue, we synthesized nicotinamide riboside trioleate chloride (NRTOCl) as a new hydrophobic nicotinamide riboside (NR) derivative. Contrary to NRCl, NRTOCl is soluble in an oil phase. The results of stability studies showed that NRTOCl was much more stable than NRCl both in water and in oil-in-water emulsions at 25 °C and 35 °C. Finally, we evaluated the bioavailability of NRTOCl by studying its digestibility in simulated intestinal fluid. The results demonstrated that NRTOCl was partially digestible and released NR in the presence of porcine pancreatin in a simulated intestinal fluid. This study showed that NRTOCl has the potential to be used as an NR derivative in ready-to-drink (RTD) beverages and other foods and supplement applications.
Leptin and Metabolic Programming
Authors: Picó Catalina , Palou Mariona
Published: December 2021

This Special Issue of Nutrients “Leptin and Metabolic Programming” includes one review article regarding the function of leptin throughout the entire life on cardiometabolic fates and four original articles related to the new function of leptin present in milk and liquid amniotic, its possible relation with other components of breast milk, and how environmental conditions may impact on leptin action and metabolic programming [...]
Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats
Authors: Dischinger Ulrich , Heckel Tobias , Bischler Thorsten , Hasinger Julia , Königsrainer Malina , Schmitt-Böhrer Angelika , Otto Christoph , Fassnacht Martin , Seyfried Florian , Hankir Mohammed Khair
Published: December 2021

Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing. Results: While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK–STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.
Roseburia hominis Increases Intestinal Melatonin Level by Activating p-CREB-AANAT Pathway
Authors: Song Lijin , He Meibo , Sun Qinghua , Wang Yujing , Zhang Jindong , Fang Yuan , Liu Shuangjiang , Duan Liping
Published: December 2021

Intestinal melatonin exerts diverse biological effects on the body. Our previous research showed that the abundance of the butyrate-producing bacteria, Roseburia, is positively related to the expression of colonic mucosal melatonin. However, the detailed relationship is unclear. Therefore, we aimed to explore whether Roseburia regulates intestinal melatonin and its underlying mechanisms. Male Sprague–Dawley germfree rats were orally administered with or without Roseburia hominis. R. hominis treatment significantly increased the intestinal melatonin level. The concentrations of propionate and butyrate in the intestinal contents were significantly elevated after gavage of R. hominis. Propionate or butyrate treatment increased melatonin, 5-hydroxytryptamine (5-HT), arylalkylamine N-acetyltransferase (AANAT), and phosphorylated cAMP-response element-binding protein (p-CREB) levels. When pretreated with telotristat ethyl, the inhibitor of tryptophan hydroxylase (TPH), or siRNA of Aanat, or 666-15, i.e., an inhibitor of CREB, propionate, or butyrate, could not promote melatonin production in the pheochromocytoma cell line BON-1. Metabolomics analysis showed that propionate and butyrate stimulation regulated levels of some metabolites and some metabolic pathways in BON-1 cell supernatants. In conclusion, propionate and butyrate, i.e., metabolites of R. hominis, can promote intestinal melatonin synthesis by increasing 5-HT levels and promoting p-CREB-mediated Aanat transcription, thereby offering a potential target for ameliorating intestinal diseases.
NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion
Authors: Herz Hussein , Song Yang , Ye Yuanchao , Tian Liping , Linden Benjamin , Abu El Haija Marwa , Chu Yi , Grobe Justin L. , Lengeling Randall W. , Mokadem Mohamad
Published: December 2021

Background/Aim: Given their widespread use and their notorious effects on the lining of gut cells, including the enteroendocrine cells, we explored if chronic exposure to non-steroidal anti-inflammatory drugs (NSAIDs) affects metabolic balance in a mouse model of NSAID-induced enteropathy. Method: We administered variable NSAIDs to C57Blk/6J mice through intragastric gavage and measured their energy balance, glucose hemostasis, and GLP-1 levels. We treated them with Exendin-9 and Exendin-4 and ran a euglycemic-hyperinsulinemic clamp. Results: Chronic administration of multiple NSAIDs to C57Blk/6J mice induces ileal ulcerations and weight loss in animals consuming a high-fat diet. Despite losing weight, NSAID-treated mice exhibit no improvement in their glucose tolerance. Furthermore, glucose-stimulated (glucagon-like peptide -1) GLP-1 is significantly attenuated in the NSAID-treated groups. In addition, Exendin-9—a GLP-1 receptor antagonist—worsens glucose tolerance in the control group but not in the NSAID-treated group. Finally, the hyper-insulinemic euglycemic clamp study shows that endogenous glucose production, total glucose disposal, and their associated insulin levels were similar among an ibuprofen-treated group and its control. Exendin-4, a GLP-1 receptor agonist, reduces insulin levels in the ibuprofen group compared to their controls for the same glucose exchange rates. Conclusions: Chronic NSAID use can induce small intestinal ulcerations, which can affect intestinal GLP-1 production, hepatic insulin sensitivity, and consequently, hepatic glucose production.
Cross-Sectional Association of Food Source with Food Insecurity, Dietary Diversity and Body Mass Index in Western Kenya
Authors: Olatunji Elizabeth , Obonyo Charles , Wadende Pamela , Were Vincent , Musuva Rosemary , Lwanga Charles , Turner-Moss Eleanor , Pearce Matthew , Mogo Ebele R. I. , Francis Oliver , Foley Louise
Published: December 2021

The triple burden of malnutrition in many low- and middle-income countries (LMICs) is partly a result of changing food environments and a shift from traditional diets to high-calorie Western-style diets. Exploring the relationship between food sources and food- and nutrition-related outcomes is important to understanding how changes in food environments may affect nutrition in LMICs. This study examined associations of household food source with household food insecurity, individual dietary diversity and individual body mass index in Western Kenya. Interview-administered questionnaire and anthropometric data from 493 adults living in 376 randomly-selected households were collected in 2019. Adjusted regression analyses were used to assess the association of food source with measures of food insecurity, dietary diversity and body mass index. Notably, participants that reported rearing domesticated animals for consumption (‘own livestock’) had lower odds of moderate or severe household food insecurity (odds ratio (OR) = 0.29 (95% CI: 0.09, 0.96)) and those that reported buying food from supermarkets had lower odds of moderate or severe household food insecurity (borderline significant, OR = 0.37 (95% CI: 0.14, 1.00)), increased dietary diversity scores (Poisson coefficient = 0.17 (95% CI: 0.10, 0.24)) and higher odds of achieving minimum dietary diversity (OR = 2.84 (95% CI: 1.79, 4.49)). Our findings provide insight into the relationship between food environments, dietary patterns and nutrition in Kenya, and suggest that interventions that influence household food source may impact the malnutrition burden in this context.
Association between Dietary Factors and Constipation in Adults Living in Luxembourg and Taking Part in the ORISCAV-LUX 2 Survey
Authors: Rollet Maurane , Bohn Torsten , Vahid Farhad ,   on behalf of the ORISCAV Working Group
Published: December 2021

Constipation, a disorder of bowel movements, is among the most frequent gastrointestinal complaints in Western countries. Dietary constituents such as inadequate fiber intake have been related to constipation, but discrepancies exist in the findings regarding dietary factors. This study investigated the association between dietary patterns and bowel movements in adults living in Luxembourg. Data from 1431 participants from ORISCAV-LUX 2 (a cross-sectional survey) who completed a 174-item food frequency questionnaire (FFQ) were analyzed. A questionnaire-based constipation score was assessed by a validated scoring system. Confounders such as physical activity and serum/urine indicators were assessed. Women had higher constipation scores than men (p < 0.001). In food group-based regression models, a negative association was found between higher constipation score and intake of grains (Beta = −0.62, 95%CI: −1.18, −0.05) and lipid-rich foods (Beta = −0.84, 95%CI: −1.55, −0.13), while a positive association was found for sugary products (Beta = 0.54, 95%CI: 0.11, 0.97) (p < 0.05). In a nutrient-based regression model, a positive association was found between constipation score and total energy (Beta = 5.24, 95%CI: 0.37, 10.11) as well as sodium intake (Beta = 2.04, 95%CI: 0.21, 3.87), and a negative one was found for total fats (Beta = −4.17, 95%CI: −7.46, −0.89) and starch (Beta = −2.91, 95%CI: −4.47, −1.36) (p < 0.05). Interestingly, neither fruits and vegetables or dietary fiber were significantly associated with constipation. Thus, grains, lipid-rich foods, total fats and starch were associated with a lower constipation score, while sugary products, sodium, and higher energy intake were correlated with higher constipation.
Thienopyrimidine: A Promising Scaffold to Access Anti-Infective Agents
Authors: Lagardère Prisca , Fersing Cyril , Masurier Nicolas , Lisowski Vincent
Published: December 2021

Thienopyrimidines are widely represented in the literature, mainly due to their structural relationship with purine base such as adenine and guanine. This current review presents three isomers—thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and thieno[3,4-d]pyrimidines—and their anti-infective properties. Broad-spectrum thienopyrimidines with biological properties such as antibacterial, antifungal, antiparasitic and antiviral inspired us to analyze and compile their structure–activity relationship (SAR) and classify their synthetic pathways. This review explains the main access route to synthesize thienopyrimidines from thiophene derivatives or from pyrimidine analogs. In addition, SAR study and promising anti-infective activity of these scaffolds are summarized in figures and explanatory diagrams. Ligand–receptor interactions were modeled when the biological target was identified and the crystal structure was solved.
Let-7i-5p Mediates the Therapeutic Effects of Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells on Mitigating Endotoxin-Induced Mortality and Liver Injury in High-Fat Diet-Induced Obese Mice
Authors: Chang Chao-Yuan , Chen Kung-Yen , Shih Hung-Jen , Chiang Milton , Huang I-Tao , Huang Yen-Hua , Huang Chun-Jen
Published: December 2021

Obesity complicates sepsis and increases the mortality of sepsis. We examined the effects of exosomes (from human placenta choriodecidual membrane-derived mesenchymal stem cells, pcMSCs) on preventing sepsis in obesity and the mitigating role of hsa-let-7i-5p microRNA. Obese mice (adult male C57BL/6J mice fed a high-fat diet for 12 weeks) received normal saline (HFD), endotoxin (10 mg/kg, intraperitoneal (ip); HFDLPS), endotoxin with exosomes (1 × 108 particles/mouse, ip; HLE), or endotoxin with let-7i-5p microRNA inhibitor-pretreated exosomes (1 × 108 particles/mouse, ip; HLEi). Our data demonstrated that the 48-h survival rate in the HLE (100%) group was significantly higher than in the HFDLPS (50%) and HLEi (58.3%) groups (both p < 0.05). In the surviving mice, by contrast, levels of liver injury (injury score, plasma aspartate transaminase and alanine transaminase concentrations, tissue water content, and leukocyte infiltration in liver tissues; all p < 0.05), inflammation (nuclear factor-κB activation, hypoxia-inducible factor-1α activation, macrophage activation, and concentrations of tumor necrosis factor-α, interleukin-6, and leptin in liver tissues; all p < 0.05), and oxidation (malondialdehyde in liver tissues, with p < 0.001) in the HLE group were significantly lower than in the HFDLPS group. Levels of mitochondrial injury/dysfunction and apoptosis in liver tissues in the HLE group were also significantly lower than in the HFDLPS group (all p < 0.05). Inhibition of let-7i-5p microRNA offset the effects of the exosomes, with most of the aforementioned measurements in the HLEi group being significantly higher than in the HLE group (all p < 0.05). In conclusion, exosomes mitigated endotoxin-induced mortality and liver injury in obese mice, and these effects were mediated by let-7i-5p microRNA.
Synthesis and Evaluation of 3-Halobenzo[b]thiophenes as Potential Antibacterial and Antifungal Agents
Authors: Masih Prerna J. , Kesharwani Tanay , Rodriguez Elivet , Vertudez Mia A. , Motakhaveri Mina L. , Le Terelan K. , Tran Minh Kieu T. , Cloyd Matthew R. , Kornman Cory T. , Phillips Aimee M.
Published: December 2021

The global health concern of antimicrobial resistance has harnessed research interest to find new classes of antibiotics to combat disease-causing pathogens. In our studies, 3-halobenzo[b]thiophene derivatives were synthesized and tested for their antimicrobial activities using the broth microdilution susceptibility method. The 3-halo substituted benzo[b]thiophenes were synthesized starting from 2-alkynyl thioanisoles using a convenient electrophilic cyclization methodology that utilizes sodium halides as the source of electrophilic halogens when reacted along with copper(II) sulfate. This environmentally benign methodology is facile, uses ethanol as the solvent, and results in 3-halo substituted benzo[b]thiophene structures in very high yields. The cyclohexanol-substituted 3-chloro and 3-bromobenzo[b]thiophenes resulted in a low MIC of 16 µg/mL against Gram-positive bacteria and yeast. Additionally, in silico absorption, distribution, metabolism, and excretion (ADME) properties of the compounds were determined. The compounds with the lowest MIC values showed excellent drug-like properties with no violations to Lipinski, Veber, and Muegge filters. The time-kill curve was obtained for cyclohexanol-substituted 3-chlorobenzo[b]thiophenes against Staphylococcus aureus, which showed fast bactericidal activity at MIC.
Thermosensitive Poly(DHSe/PEG/PPG Urethane)-Based Hydrogel Extended Remdesivir Application in Ophthalmic Medication
Authors: Xu Sennan , Ke Lingjie , Zhao Sichen , Li Zhiguo , Xiao Yang , Wu Yunlong , Ren Jie , Qiu Yan
Published: December 2021

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.
Polydatin Alleviates Diabetes-Induced Hyposalivation through Anti-Glycation Activity in db/db Mouse
Authors: Kim Hyung Rae , Jung Woo Kwon , Park Su-Bin , Ryu Hwa Young , Kim Yong Hwan , Kim Junghyun
Published: December 2021

Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanuts, grapes, and red wine, and is known to have antiglycation, antioxidant, and anti-inflammatory effects. Diabetes mellitus is a very common disease, and diabetic complications are very common complications. The dry mouth symptom is one of the most common oral complaints in patients with diabetes mellitus. Diabetes mellitus is thought to promote hyposalivation. In this study, we aimed to investigate the improvement effect of polydatin on diabetes-induced hyposalivation in db/db mouse model of type 2 diabetes. We examined salivary flow rate, TUNEL assay, PAS staining, and immunohistochemical staining for AGEs, RAGE, HMGB1, 8-OHdG, and AQP5 to evaluate the efficacy of polydatin in the submandibular salivary gland. Diabetic db/db mice had a decreased salivary flow rate and salivary gland weight. The salivary gland of the vehicle-treated db/db mice showed an increased apoptotic cell injury. The AGEs were highly accumulated, and its receptor, RAGE expression was also enhanced. Expressions of HMGB1, an oxidative cell damage marker, and 8-OHdG, an oxidative DNA damage marker, increased greatly. However, polydatin ameliorated this hypofunction of the salivary gland and inhibited diabetes-related salivary cell injury. Furthermore, polydatin improved mucin accumulation, which is used as a damage marker for salivary gland acinar cells, and decreased expression of water channel AQP5 was improved by polydatin. In conclusion, polydatin has a potent protective effect on diabetes-related salivary gland hypofunction through its antioxidant and anti-glycation activities, and its AQP5 upregulation. This result suggests the possibility of the use of polydatin as a therapeutic drug to improve hyposalivation caused by diabetes.
Folic Acid-Decorated β-Cyclodextrin-Based Poly(ε-caprolactone)-dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy
Authors: Yang Huikang , Wang Nianhua , Yang Ruimeng , Zhang Liming , Jiang Xinqing
Published: December 2021

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.