bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Possible Antioxidant, Anti-Hyperglycaemic, Anti-Alzheimer and Anti-Inflammatory Effects of Teucrium polium Aerial Parts (Lamiaceae)
Authors: Benchikha Naima , Messaoudi Mohammed , Larkem Imane , Ouakouak Hamza , Rebiai Abdelkrim , Boubekeur Siham , Ferhat Mohamed Amine , Benarfa Adel , Begaa Samir , Benmohamed Mokhtar , Almasri Diena M. , Hareeri Rawan H. , Youssef Fadia S.
Published: October 2022

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 μg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 μg/mL and mild activity in the β-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 μg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 μg GAE/mg) and flavonoids (24.30 ± 0.44 μg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research.
Design of Random Warranty and Maintenance Policy: From a Perspective of the Life Cycle
Authors: Shang Lijun , Yu Xiguang , Wang Liying , Du Yongjun
Published: October 2022

Driven by digital technologies, it is possible that high-tech equipment management personnel use monitored job cycles to ensure products’ operation and maintenance over their life cycle. By means of monitored job cycles, this paper designs two categories of random maintenance policies: a two-stage two-dimensional free repair warranty (2DFRW) policy and a random hybrid periodic replacement (RHPR) policy. The 2DFRW policy is performed to ensure the product’s operation and maintenance over the warranty stage. Under such a policy, a product is minimally repaired at each failure, and regions of the second-stage warranty are set to be diverse to remove all inequities produced by limitations of the first-stage warranty. The warranty cost of two-stage 2DFRW is built and discussed. The RHPR policy is modeled to ensure the product’s operation and maintenance over the post-warranty stage. Under this policy, depending on the final expiry of the two-stage 2DFRW, a bivariate random periodic replacement (BRPR) policy and a univariate random periodic replacement (URPR) policy are skillfully used to reduce the maintenance cost over the post-warranty stage and maximally extend the residual useful time of the product through the warranty. The expected cost rate over the product’s operation and maintenance cycle is derived on the basis of renewal rewarded theorem. The optimal RHPR policy is analyzed by minimizing the cost rate. The presented models are numerically analyzed to explore hidden characteristics.
The Changes in Size of Periapical Lesions after Root Canal Treatments Assessed by Digital Periapical Radiography and Cone-Beam Computed Tomography: A 2-Years Prospective Clinical Study
Authors: Gudac Jelena , Hellén-Halme Kristina , Maciulskiene Vita
Published: October 2022

Background and Objectives: There is limited information regarding comparison of long-term dynamics of periapical bone destruction estimated by digital periapical radiography (DPR) and by cone-beam computed tomography (CBCT). This study aimed to compare the radiographically assessed periapical changes of endodontically treated teeth over 2 years of follow-up and to analyse disagreements in periapical lesion size estimates around the same roots using DPR and CBCT. Materials and Methods: A total of 176 endodontically treated teeth, of 128 patients with apical periodontitis, were assessed by DPR and CBCT, at baseline and after 2 years. All periapical radiolucencies were categorised by severity (S0, S1, S2, S3) concerning their size. Descriptive statistics were used to report distribution of the radiolucencies at baseline and at follow-up, and their size transitions over 2 years. Site-specific comparison of the radiolucencies identified by two methods was performed using Z test and Pearson’s chi-square test. Results: majority of the detected radiolucencies were scored as S0: 65% and 68% at baseline; 89% and 83% at follow-up, by DPR and CBCT, respectively. Site-specific score comparison showed that disagreements comprised 18% and 20% of the total number of radiolucencies detected by DPR and CBCT, respectively. There were more disagreements between DPR and CBCT within categories S1 and S2 + S3 compared to S0: at baseline, they comprised 17–33% and after two years 62–95% of all detected radiolucencies within the category. 65% of non-matching score transitions over two years occurred between S0 and S1. The CBCT-based evaluation resulted in negative treatment outcomes for 10 more root canals than the DPR-based result. Conclusions: Most remarkable disagreement between DPR and CBCT recordings was observed within the radiolucency categories S2 and S3. However, the diagnostic accuracy of both radiographic methods was questionable as it resulted in a high proportion of non-matching S0-S1 lesion transitions over 2 years.
Physical Activity in the Elderly and Frailty Syndrome: A Retrospective Study in Primary Care
Authors: Zulfiqar Abrar-Ahmad , Habchi Habib , Habchi Perla , Dembele Ibrahima Amadou , Andres Emmanuel
Published: October 2022

Objectives: Physical activity carries numerous therapeutic benefits, and it is more effective when applied before the onset of symptoms. The objective of this study is to compare the correlation of the evaluation of physical activity carried out using the Ricci and Gagnon test and the frailty profile measured by the mSEGA scale in a population of patients consulting in general medicine. Methods: We conducted a retrospective study within a general practitioner clinic in Chaumont and Bologne (Haute-Marne department) during a 3-month period. Patients aged 65 years and up were screened for frailty using the modified SEGA (mSEGA) assessment, and physical activity was measured using the Ricci–Gagnon questionnaire. Results: A total of 44 patients were selected, with a slightly female predominance (59.1%). Of these, 21 patients reported having worked in manual labor. Seven patients were found to be frail using the SEGAm assessment, while 10 (22.73%) patients had an inactive profile according the Ricci–Gagnon score. Malnutrition was detected in six patients (13.64%) using the MNA survey. Frailty as defined by the mSEGA scale had no statistical correlation (p = 0.68) with the Ricci–Gagnon score. A Ricci–Gagnon inactive profile showed statistical correlations with fall indicators (unipedal balance test, p = 0.014) and malnutrition scores using the MNA (p = 0.0057) as well as with the Charlson Comorbidity Index (p = 0.027). Conclusion: A systematic survey of the elderly by a general practitioner implementing a regular and suitable physical activity regimen would allow a better screening of frailty, minimizing its complications.
Metabolome-Wide Associations of Gestational Weight Gain in Pregnant Women with Overweight and Obesity
Authors: Dai Jin , Boghossian Nansi S. , Sarzynski Mark A. , Luo Feng , Sun Xiaoqian , Li Jian , Fiehn Oliver , Liu Jihong , Chen Liwei
Published: October 2022

Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. This metabolome-wide association study aimed to identify metabolomic markers for GWG. This longitudinal study included 39 Black and White pregnant women with a prepregnancy body mass index (BMI) of ≥ 25 kg/m2. Untargeted metabolomic profiling was performed using fasting plasma samples collected at baseline (mean: 12.1 weeks) and 32 weeks of gestation. The associations of metabolites at each time point and changes between the two time points with GWG were examined by linear and least absolute shrinkage and selection operator (LASSO) regression analyses. Pearson correlations between the identified metabolites and cardiometabolic biomarkers were examined. Of the 769 annotated metabolites, 88 metabolites at 32 weeks were individually associated with GWG, with four (phosphatidylcholine (PC) 34:4, triacylglycerol (TAG) 52:6, arachidonic acid, isoleucine) jointly associated with GWG (area under the receiver operating characteristic curve (AUC) for excessive GWG: 0.80, 95% CI: 0.67, 0.93). No correlations were observed between the 88 metabolites and insulin, C-peptide, and high-sensitivity C-reactive protein at 32 weeks. Twelve metabolites at baseline (AUC for excessive GWG: 0.80, 95% CI: 0.62, 0.99) and three metabolite changes (AUC for excessive GWG: 0.73, 95% CI: 0.44, 1.00) were jointly associated with GWG. We identified novel metabolites in the first and third trimesters associated with GWG, which may shed light on the pathophysiology of GWG.
Distribution and Molecular Characteristics of Vibrio Species Isolated from Aquatic Environments in China, 2020
Authors: Xiao Yue , Huang Zhenzhou , Yu Keyi , Wang Maoshu , Gao He , Bai Xuemei , Jiang Mengnan , Wang Duochun
Published: October 2022

To understand the characteristics of Vibrio isolates in aquatic environments in China and their public health significance, this study investigated water samples in six cities in China in 2020. A total of 88 sampling locations were included and Vibrio isolates were identified in 81 of them. A total of 143 Vibrio isolates belonging to 16 species were selected for characterization. The population structure of Vibrio species showed great differences among the six cities, indicating regional specificity. The presence of virulence genes was examined for the isolates (n = 78) of five pathogenic Vibrio species. All isolates except one (n = 77) contained at least one virulence gene and isolates belonging to the same species showed very similar virulence gene profiles. Then, 26 isolates from 12 species were examined by multilocus sequence typing and were assigned to 25 STs, of which 24 STs were new. Also, the presence of antibiotic-resistant genes was investigated for all 143 isolates and only three isolates were found to contain genes from aminoglycosides, phenicols, beta-lactams or the tetracycline family. Our results provide valuable insights into the Vibrio community in Chinese aquatic environments and can be applied as guidance for the environmental surveillance of the risk of Vibrio isolates.
Gut Microbiota Profiles in Children and Adolescents with Psychiatric Disorders
Authors: Soltysova Marcela , Tomova Aleksandra , Ostatnikova Daniela
Published: October 2022

The aim of our work is to summarize the current state of knowledge on gut microbiota differences in children and adolescents with psychiatric disorders. To find the relevant articles, the PubMed, Web of Science, and Google Scholar databases were searched. Articles in English presenting original data and comparing the composition of gut microbiota in child psychiatric patients with gut microbiota in healthy children and adolescents were selected. Finally, we identified 55 articles eligible for our purpose. The majority of patients with autism spectrum disorders (ASD) were investigated. A smaller number of studies evaluating the gut microbiota in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), Rett syndrome, anorexia nervosa, depressive disorder (DD), and tic disorders were found. The main findings of this research are discussed in our review, focusing on the age-related gut microbiota specificity for psychiatric disorders and the differences between individual diagnosis. To conclude, the gut microbiota in children and adolescents with psychiatric disorders is evidently different from that in controls. The most pronounced differences are seen in children with ASD, less in ADHD. Moreover, the changes are not identical to those in adult psychiatric patients, as Ruminococcus, Turicibacter, and Bilophila were increased in adults, and decreased in children with ASD, and Parabacteroides and Alistipes were more frequently represented in adults, but less frequently represented in children with depression. The available data suggest some genera have a different abundance in individual psychiatric disorders (e.g., Bilophila, Bifidobacterium, Clostridium, Coprococcus, Faecalibacterium, and Ruminococcus), suggesting their importance for the gut–brain axis. Other bacterial genera might be more important for the pathophysiology of specific disorder in children and adolescents, as Akkermansia and Desulfovibrio for ASD, or Romboutsia for DD. Based on the research findings, we assume that gut microbiota corrections have the potential to improve clinical symptoms in psychiatric patients.
High Environmental Radioactivity in Artisanal and Small-Scale Gold Mining in Eastern Democratic Republic of the Congo
Authors: Atibu Emmanuel K. , Arpagaus Philippe , Mulaji Crispin K. , Mpiana Pius T. , Poté John , Loizeau Jean-Luc , Carvalho Fernando P.
Published: October 2022

The radioactivity associated with artisanal and small-scale gold mining activities (ASM) carried out along the Ulindi River, in the eastern Democratic Republic of the Congo, was evaluated by gamma-ray spectrometry and inductively coupled plasma–mass spectrometry of soil and sediment samples. The results revealed that activity concentrations of 238U (up to 3127 ± 98 Bq kg−1), 226Ra (up to 2710 ± 89 Bq kg−1) and 232Th (up to 2142 ± 162 Bq kg−1) were 71- to 89-fold higher than the worldwide average concentrations reported by UNSCEAR in soils. Primordial radionuclides are, thus, present in high concentrations in deposits of gold in that region and the average ambient effective radiation dose rate was determined at 8.4 mSv y−1 (range 0.5 to 40 mSv y−1). This area may be classified as a natural high background radiation area (HBRA). The radiation risk for artisanal miners and population members manipulating those geological materials were assessed through radiological parameters. such as the radium equivalent activity index (RaEq), outdoor gamma absorbed dose rate (ODRA), annual effective dose equivalent (AEDE), and excess lifetime cancer risk (ELCR). The mean values of these parameters were significantly elevated in comparison to the world average levels and indicated the existence of significant radiation risks for gold miners and members of the local population. A radiation safety policy seems needed to protect workers and the local population in this region.
The Role of Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy
Authors: Hayashi Daiki , Shirai Yasuhito
Published: October 2022

The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients’ quality of life and medical expenses. Furthermore, there are limited drugs for treating diabetic nephropathy patients. Impaired lipid signaling, especially abnormal protein kinase C (PKC) activation by de novo-synthesized diacylglycerol (DG) under high blood glucose, is one of the causes of diabetic nephropathy. DG kinase (DGK) is an enzyme that phosphorylates DG and generates phosphatidic acid, i.e., DGK can inhibit PKC activation under diabetic conditions. Indeed, it has been proven that DGK activation ameliorates diabetic nephropathy. In this review, we summarize the involvement of PKC and DGK in diabetic nephropathy as therapeutic targets, and its mechanisms, by referring to our recent study.
Modulating the Inclusive and Coordinating Ability of Thiacalix[4]arene and Its Antenna Effect on Yb3-Luminescence via Upper-Rim Substitution+
Authors: Podyachev Sergey N. , Sudakova Svetlana N. , Zairov Rustem R. , Syakaev Victor V. , Masliy Alexey N. , Dusek Michal , Gubaidullin Aidar T. , Dovzhenko Alexey P. , Buzyurova Daina N. , Lapaev Dmitry V. , Mambetova Gulnaz Sh. , Babaev Vasily M. , Kuznetsov Andrey M. , Mustafina Asiya R.
Published: October 2022

The present work introduces the series of thiacalix[4]arenes (H4L) bearing different upper-rim substituents (R = H, Br, NO2) for rational design of ligands providing an antenna-effect on the NIR Yb3+-centered luminescence of their Yb3+ complexes. The unusual inclusive self-assembly of H3L− (Br) through Brπ interactions is revealed through single-crystal XRD analysis. Thermodynamically favorable formation of dimeric complexes [2Yb3+:2HL3−] leads to efficient sensitizing of the Yb3+ luminescence for H4L (Br, NO2), while poor sensitizing is observed for ligand H4L (H). X-ray analysis of the single crystal separated from the basified DMF solutions of YbCl3 and H4L(NO2) has revealed the transformation of the dimeric complexes into [4Yb3+:2L4−] ones with a cubane-like cluster structure. The luminescence characteristics of the complexes in the solutions reveal the peculiar antenna effect of H4L(R = NO2), where the triplet level at 567 nm (17,637 cm−1) arisen from ILCT provides efficient sensitizing of the Yb3+ luminescence.
Preparation and Characterization of Magnetic Metal–Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase
Authors: Li Moju , Dai Xusheng , Li Aifeng , Qi Qi , Wang Wenhui , Cao Jia , Jiang Zhenting , Liu Renmin , Suo Hongbo , Xu Lili
Published: October 2022

Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal–organic framework composite, IL-Fe3O4@UiO-66-NH2, was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe3O4@UiO-66-NH2) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe3O4@UiO-66-NH2 was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe3O4@UiO-66-NH2 reached 74.4%, which was higher than that of PPL-Fe3O4@UiO-66-NH2 (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe3O4@UiO-66-NH2 had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe3O4@UiO-66-NH2 modified by ionic liquids has great potential for immobilized enzymes.
Enantioselective, Decarboxylative (3+2)-Cycloaddition of Azomethine Ylides and Chromone-3-Carboxylic Acids
Authors: Kowalska Ewelina , Sieroń Lesław , Albrecht Anna
Published: October 2022

Herein, we describe the synthesis of a variety of chiral hybrid pyrrolidine-chromanone polycyclic derivatives. A convenient (3+2)-annulation of azomethine ylides with chromone-3-carboxylic acid realized under Brønsted base catalysis produced highly functionalized products in high yields with good stereoselectivities through asymmetric, intermolecular, and decarboxylative (3+2)-cyclization.
Itraconazole-Induced Increases in Gilteritinib Exposure Are Mediated by CYP3A and OATP1B
Authors: Garrison Dominique A. , Jin Yan , Talebi Zahra , Hu Shuiying , Sparreboom Alex , Baker Sharyn D. , Eisenmann Eric D.
Published: October 2022

Gilteritinib, an FDA-approved tyrosine kinase inhibitor approved for the treatment of relapsed/refractory FLT3-mutated acute myeloid leukemia, is primarily eliminated via CYP3A4-mediated metabolism, a pathway that is sensitive to the co-administration of known CYP3A4 inhibitors, such as itraconazole. However, the precise mechanism by which itraconazole and other CYP3A-modulating drugs affect the absorption and disposition of gilteritinib remains unclear. In the present investigation, we demonstrate that pretreatment with itraconazole is associated with a significant increase in the systemic exposure to gilteritinib in mice, recapitulating the observed clinical drug–drug interaction. However, the plasma levels of gilteritinib were only modestly increased in CYP3A-deficient mice and not further influenced by itraconazole. Ensuing in vitro and in vivo studies revealed that gilteritinib is a transported substrate of OATP1B-type transporters, that gilteritinib exposure is increased in mice with OATP1B2 deficiency, and that the ability of itraconazole to inhibit OATP1B-type transport in vivo is contingent on its metabolism by CYP3A isoforms. These findings provide new insight into the pharmacokinetic properties of gilteritinib and into the molecular mechanisms underlying drug–drug interactions with itraconazole.
Boosting the Photocatalytic Ability of TiO2 Nanosheet Arrays for MicroRNA-155 Photoelectrochemical Biosensing by Titanium Carbide MXene Quantum Dots
Authors: Yan Bingdong , Cheng Zike , Lai Caiyan , Qiao Bin , Yuan Run , Zhang Chide , Pei Hua , Tu Jinchun , Wu Qiang
Published: October 2022

The electrodes of two-dimensional (2D) titanium dioxide (TiO2) nanosheet arrays were successfully fabricated for microRNA-155 detection. The (001) highly active crystal face was exposed to catalyze signaling molecules ascorbic acid (AA). Zero-dimensional (0D) titanium carbide quantum dots (Ti3C2Tx QDs) were modified to the electrode as co-catalysts and reduced the recombination rate of the charge carriers. Spectroscopic methods were used to determine the band structure of TiO2 and Ti3C2Tx QDs, showing that a type Ⅱ heterojunction was built between TiO2 and Ti3C2Tx QDs. Benefiting the advantages of materials, the sensing platform achieved excellent detection performance with a wide liner range, from 0.1 pM to 10 nM, and a low limit of detection of 25 fM (S/N = 3).
Terahertz Modulation and Ultrafast Characteristic of Two-Dimensional Lead Halide Perovskites
Authors: Liu Hongyuan , He Xunjun , Ren Jie , Jiang Jiuxing , Yao Yongtao , Lu Guangjun
Published: October 2022

In recent years, two-dimensional (2D) halide perovskites have been widely used in solar cells and photoelectric devices due to their excellent photoelectric properties and high environmental stability. However, the terahertz (THz) and ultrafast responses of the 2D halide perovskites are seldom studied, limiting the developments and applications of tunable terahertz devices based on 2D perovskites. Here, 2D R-P type (PEA)2(MA)2Pb3I10 perovskite films are fabricated on quartz substrates by a one-step spin-coating process to study their THz and ultrafast characteristics. Based on our homemade ultrafast optical pump–THz probe (OPTP) system, the 2D perovskite film shows an intensity modulation depth of about 10% and an ultrafast relaxation time of about 3 ps at a pump power of 100 mW due to the quantum confinement effect. To further analyze the recombination mechanisms of the photogenerated carriers, a three-exponential function is used to fit the carrier decay processes, obtaining three different decay channels, originating from free carrier recombination, exciton recombination, and trap-assisted recombination, respectively. In addition, the photoconductor changes (∆σ) at different pump–probe delay times are also investigated using the Drude-Smith model, and a maximum difference of 600 S/m is obtained at τp = 0 ps for a pump power of 100 mW. Therefore, these results show that the 2D (PEA)2(MA)2Pb3I10 film has potential applications in high-performance tunable and ultrafast THz devices.
Gut Microbiota, the Potential Biological Medicine for Prevention, Intervention and Drug Sensitization to Fight Diseases
Authors: Wu Haijie , Chen Xiaoguang , Zhang Sen , Li Jiaxin
Published: October 2022

As the largest “immune organ” of human beings, the gut microbiota is symbiotic and mutually beneficial with the human host, playing multiple physiological functions. Studies have long shown that dysbiosis of gut microbiota is associated with almost all human diseases, mainly including type II diabetes, cancers, neurodegenerative diseases, autism spectrum disorder, and kidney diseases. As a novel and potential biological medicine for disease prevention, intervention and drug sensitization, the gut microbiota has attracted more and more attention recently. Although the gut microbiota is a comprehensive microbial community, several star bacteria have emerged as possible tools to fight against various diseases. This review aims to elucidate the relevance of gut microbiota dysbiosis with disease occurrence and progression, and mainly summarizes four well-known genera with therapeutic and sensitizing potential, Akkermansia, Bifidobacterium, Lactobacillus and Parabacteroides, thoroughly elucidate their potential value as biological drugs to treat diverse disease.
Associations between Healthy Lifestyle and All-Cause Mortality in Individuals with Metabolic Associated Fatty Liver Disease
Authors: Wang Xinyu , Wang Aruna , Zhang Ruosu , Cheng Si , Pang Yuanjie
Published: October 2022

Background and Aims: There is limited evidence about the association of healthy lifestyle and all-cause mortality in individuals with metabolic associated fatty liver disease (MAFLD). We aimed to examine this association and compare it with the association in those without MAFLD. Methods: A prospective cohort study was performed and linked mortality data through 2019 in the National Health Nutrition Examination Survey (NHANES 1999–2010). A healthy lifestyle score was constructed from cigarette smoking, alcohol drinking, healthy eating score, and leisure-time physical activity. Risk stratification was conducted in participants with MAFLD by fibrosis biomarkers and liver enzymes. Survey-weight adjusted Cox regression was used to estimate adjusted hazard ratios (HRs) and confidence intervals (CIs) for all-cause mortality associated with healthy lifestyle. Results: There was a protective association between healthy lifestyle and all-cause mortality in participants with MAFLD (HR per 1-unit increase of healthy lifestyle score 0.77 [95% CI 0.69–0.85]), with no difference from the association in participants without MAFLD (HR 0.77 [0.72–0.82]). In participants with MAFLD, the associations tended to be stronger in those with lower risk of advanced fibrosis (HR per 1-unit increase of healthy lifestyle score 0.64 [0.50–0.79] for low NAFLD fibrosis score [NFS] and 0.84 [0.75–0.93] for high NFS, p-value for interaction 0.02), but did not differ by liver enzymes. The results for non-alcoholic fatty liver disease (NAFLD) mirrored those for MAFLD. Conclusions: Healthy lifestyle showed protective associations with all-cause mortality regardless of MAFLD status, and the associations tended to be stronger in those with lower risk of advanced fibrosis. Timely lifestyle modification matters for individuals with MAFLD.
Lower Rate of Water Absorption of an Oral Rehydration Solution with Partially Hydrolyzed Guar Gum in Conscious Rats
Authors: Takahashi Toru , Tokunaga Miki , Okubo Tsutomu , Ozeki Makoto , Kapoor Mahendra P. , Yasukawa Zenta
Published: October 2022

The purpose of the present study was to elucidate the rate of water absorption of an oral rehydration solution containing partially hydrolyzed guar gum (PHGG) in the small intestine, which is the main site of water absorption when water is drunk. Seven-week-old male SD rats were employed. We prepared four types of an aqueous solution, i.e., containing mineral and sugar, containing PHGG, containing mineral and sugar and PHGG, or containing no additives. After 24 h of food and 4 h of water deprivation, the aqueous solutions were infused into the stomach of conscious rats on their hands using a syringe with a stomach sonde. We sampled the stomach and the small intestine with contents 8 min after the infusions. Causal effects were calculated using a Bayesian network. PHGG increased the residual amount of water in the gastro-intestine, which depends negatively on the absorption of water in the small intestine/the flow rate to the small intestine. The absorption of water in the small intestine depended positively on the flow rate to the small intestine, which depended negatively on the free water in the solutions. PHGG decreased water absorption in the small intestine by decreasing the free water in the aqueous solutions.
Phytate Hydrolysate Differently Modulates the Immune Response of Human Healthy and Cancer Colonocytes to Intestinal Bacteria
Authors: Markiewicz Lidia Hanna , Ogrodowczyk Anna Maria , Wiczkowski Wiesław , Wróblewska Barbara
Published: October 2022

(1) Phytic acid (PA) is a component of cereal seeds and legumes, therefore its consumption is much higher in a vegan and vegetarian diet compared to a conventional diet. The diet is the main driver of metabolic activity of gut microbiota, therefore, the ability to degrade phytates by the microbiota of vegans significantly exceeds that of the gut microbiota of omnivores. The aim of the study was to investigate the early phase of the immune response of colonocytes treated with an enzymatic hydrolysate of phytic acid (hPA120) and gut bacteria. (2) Cell lines derived from healthy (NCM460D) and cancer (HCT116) colonic tissue and fecal bacteria from vegan (V) and omnivorous (O) donors were investigated. Fecal bacteria were grown in mucin and phytic acid supplemented medium. Cultured bacteria (BM) were loaded onto colonocytes alone (V BM and O BM) or in combination with the phytate hydrolysate (V BM + hPA120 and O BM + hPA120). After a treatment of 2 h, bacterial adhesion, secretion of cytokines, and the expression of genes and proteins important for immune response were determined. (3) All bacteria-treated colonocytes increased the expression of IL8 compared to controls. The significant increase of the secreted IL-8 (p < 0.01) in both cell lines was observed for O BM and O BM + hPA120. The increase of TNF, IL-1β, and IL-10 secretion in healthy colonocytes (V BM alone and with hPA120 treatments; p < 0.05) and for TNF and IL-10 in cancer cells (treatments except O BM + hPA120 and V BM, respectively; p > 0.05) were stated. A comparison of solely the effect of hPA120 on bacteria-treated colonocytes (BM vs. BM + hPA120) showed that hPA120 decreased expression of NFkB1 and TNFR (p < 0.001) in healthy colonocytes. In cancer colonocytes, the expression of TLR4 and IL1R increased after BM + hPA120 treatment, whereas the secretion of IL-8 and MYD88 and TNFR expression decreased (p < 0.01). (4) The investigated hPA120 showed a differentiated modulatory activity on the immune response of healthy and cancer human colonocytes. Especially when analyzed independently on the gut bacteria origin, it reduced the proinflammatory response of HCT116 cells to gut bacteria, while being neutral for the bacteria-treated healthy colonocytes.
Antioxidant Efficacy of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Elderly Subjects: A Randomized, Double Blind, Controlled Study
Authors: Nobile Vincenzo , Pisati Marta , Cestone Enza , Insolia Violetta , Zaccaria Vincenzo , Malfa Giuseppe Antonio
Published: October 2022

The world population is rapidly aging. This should cause us to reflect on the need to develop a new nutritional approach to mitigate the accumulation of reactive oxygen species (ROS)-induced damage. A randomized, double blind, controlled study was carried out on 60 elderly male and female subjects. Product efficacy was measured before and after 2 and 8 weeks of product intake. The reduced (GSH) and oxidized (GSSG) glutathione concentrations in the erythrocytes and the reactive oxygen metabolites (d-ROMs) hematic concentration were measured to assess the antioxidant efficacy. The tumor necrosis factor-alpha (TNF-α) levels in the serum were measured to assess the anti-inflammatory effectiveness. The wellbeing was assessed by Short Form Health Survey (SF-36) questionnaire (male) and by Menopause Rating Scale (MRS) (female). Blood, urine analysis and electrocardiography (ECG) were carried out to assess the product’s safety. The results showed that GSH/GSSG ratio increased by 22.4% and 89.0% after 2 and 8 weeks of product intake. Serum TNF-α levels decreased by 2.5% after 8 weeks of product intake. The SF-36 QoL and the MRS questionnaire outputs indicate, preliminarily, a positive effect of the extract intake in ameliorating the wellbeing of both male and female subjects. The product was well-tolerated. Our findings suggest that the test product has antioxidant and anti-inflammatory efficacy and has a positive effect on the wellbeing of elderly female and male subjects.
Association between High-Fat Diet during Pregnancy and Heart Weight of the Offspring: A Multivariate and Mediation Analysis
Authors: Wang Wenji , Huo Yu , Zhang Jialing , Xu Da , Bai Fan , Gui Yonghao
Published: October 2022

Maternal nutrition and health status in the peri-pregnancy period are closely related to offspring health. Currently, population studies are unable to provide quantitative relationships and effective measures of peri-pregnancy high-fat diet and offspring myocardial remodeling due to the difficulty of obtaining human samples. This study aimed to establish the mouse models of maternal obesity and high-fat diet supplementation and deprivation during pregnancy. The effects of obesity, periconceptional high-fat diet window, fetal weight, sex, and placental weight on myocardial remodeling in the offspring were measured by single-factor and multiple-factor regression analyses. Moreover, the relationship between perinatal high-fat diet/fetal weight and offspring myocardial remodeling was explored using the mediation analysis model. The multivariate analysis showed that the heart weight to body weight (HW/BW) ratio of the offspring decreased by −1.6525 mg/g for every 1-g increase in fetal weight. The offspring HW/BW increased by 1.1967 mg/g if pregnant women were exposed to a high-fat diet throughout pregnancy. The mediation analysis model of a perinatal high-fat diet for the myocardial remodeling of offspring revealed that fetal weight had a suppression effect on the myocardial weight of offspring, accounting for 60.70%; also, it had a mediating effect on the HW/BW of offspring, accounting for 17.10%. Moreover, subgroup analysis showed an interaction between offspring sex and HW/BW in a maternal high-fat diet during pregnancy. Additionally, a quantitative real-time polymerase chain reaction experiment further proved that a perinatal high-fat diet could change the important indicators of myocardial remodeling in offspring. In conclusion, this study found that a high-fat diet in the periconceptional period influenced factors in offspring myocardial remodeling. Moreover, maternal high-fat diet deprivation attenuated the changes in offspring myocardial remodeling. In addition, the role of fetal weight in mediating maternal high-fat diet-mediated offspring myocardial remodeling was quantified. Our study showed that a sensible and healthy diet during the perinatal period, especially during pregnancy, played a positive role in the health of the offspring.
Changes Induced by Aging and Long-Term Exercise and/or DHA Supplementation in Muscle of Obese Female Mice
Authors: Martínez-Gayo Alejandro , Félix-Soriano Elisa , Sáinz Neira , González-Muniesa Pedro , Moreno-Aliaga María J.
Published: October 2022

Obesity and aging promote chronic low-grade systemic inflammation. The aim of the study was to analyze the effects of long-term physical exercise and/or omega-3 fatty acid Docosahexaenoic acid (DHA) supplementation on genes or proteins related to muscle metabolism, inflammation, muscle damage/regeneration and myokine expression in aged and obese mice. Two-month-old C57BL/6J female mice received a control or a high-fat diet for 4 months. Then, the diet-induced obese (DIO) mice were distributed into four groups: DIO, DIO + DHA, DIO + EX (treadmill training) and DIO + DHA + EX up to 18 months. Mice fed a control diet were sacrificed at 2, 6 and 18 months. Aging increased the mRNA expression of Tnf-α and decreased the expression of genes related to glucose uptake (Glut1, Glut4), muscle atrophy (Murf1, Atrogin-1, Cas-9) and myokines (Metrnl, Il-6). In aged DIO mice, exercise restored several of these changes. It increased the expression of genes related to glucose uptake (Glut1, Glut4), fatty acid oxidation (Cpt1b, Acox), myokine expression (Fndc5, Il-6) and protein turnover, decreased Tnf-α expression and increased p-AKT/AKT ratio. No additional effects were observed when combining exercise and DHA. These data suggest the effectiveness of long-term training to prevent the deleterious effects of aging and obesity on muscle dysfunction.
Development of Quercetin-DHA Ester-Based Pectin Conjugates as New Functional Supplement: Effects on Cell Viability and Migration
Authors: Carullo Gabriele , Spizzirri Umile Gianfranco , Malivindi Rocco , Rago Vittoria , Motta Marisa Francesca , Lofaro Danilo , Restuccia Donatella , Aiello Francesca
Published: October 2022

A quercetin derivative with remarkable biological performance was successfully synthesized by chemical modification of the flavonoid with docosahexaenoic acid to synthesize 2-(2,2-diphenylbenzo[d][1,3]dioxol-5-yl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoate (3), deeply characterized by NMR spetroscopy. Modified quercetin and pectin were involved in a grafting process by an ecofriendly radical procedure able to preserve the biological features of the quercetin derivative. Antioxidant performances of the conjugate were evaluated both in term of total phenolic amount and scavenger activity in organic and aqueous environments. Additionally, in vitro acute oral toxicity was also tested against Caco-2 cells and 3T3 fibroblasts, confirming that pectin conjugate does not have any effect on cell viability at the dietary use concentrations. Finally, in vitro experiments highlighted the ability of the conjugate to counteract the migratory properties of Caco-2 and HepG2 cells, indicating its feature in the reduction of the migration of tumour cells. These data showed that the covalent binding of the quercetin derivative to the pectin chain represents a very interesting strategy to improve the bioavailability of the quercetin, representing an effective means of protecting and to transporting polyphenol molecules.
Synthesis, Characterization and Biological Investigation of New N-Modified Spinorphin Analogs
Authors: Todorov Petar , Georgieva Stela , Tchekalarova Jana , Subaer Subaer , Peneva Petia , Hartati Hartati
Published: October 2022

The emergence of diverse peptide derivatives has been due to constant efforts to find a specific peptide with pronounced biological activity for effective application as a therapeutic. Spinorphin-peptide products have been reported to possess various applications and properties. In the present study, spinorphin peptides with a rhodamine residue and a modification in the amino acid backbone were synthesized by a solid-phase method using Fmoc chemistry. The results obtained from the spectral and electrochemical techniques used: Scanning electron microscopy (SEM), UV-vis, fluorescence, infrared spectroscopy (IR), and voltammetry were used to elucidate the structural characteristics and some physicochemical properties to gain insight into their behavior in the solid state and in aqueous solutions with different pHs. Both Rh-S5 and Rh-S6 had compound anticonvulsant effect comparable to Rh-S against psychomotor seizures at the highest dose of 20 μg. Furthermore, Rh-S6 showed a strong ability to inhibit seizure propagation and had a similar threshold to Rh-S against the intravenous pentylenetetrazol induced clonic seizure in mice; one of the three hybrid spinorphin analogs tested when screened for anticonvulsant activity. Biological tests against several bacterial pathogens such as Staphylococcus aureus, Escherichia coli, and Bacillus cereus showed similar results to negative control of the new peptide derivatives. The compounds also showed weak activity against Candida albicans fungus. The antioxidant testing results revealed more than 50% activity by reviewing the radical deterrence capabilities of 2,2-diphenyl-1-picrylhydrazyl (DPPH). The results are indicative of the ongoing search for universal antimicrobial agents with pronounced synergism when used simultaneously as anticonvulsant, antibacterial, and antifungal agents.
Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat
Authors: Lagard Camille , Vodovar Dominique , Chevillard Lucie , Callebert Jacques , Caillé Fabien , Pottier Géraldine , Liang Hao , Risède Patricia , Tournier Nicolas , Mégarbane Bruno
Published: October 2022

Tramadol overdose is frequently associated with the onset of seizures, usually considered as serotonin syndrome manifestations. Recently, the serotoninergic mechanism of tramadol-attributed seizures has been questioned. This study’s aim was to identify the mechanisms involved in tramadol-induced seizures in overdose in rats. The investigations included (1) the effects of specific pretreatments on tramadol-induced seizure onset and brain monoamine concentrations, (2) the interaction between tramadol and γ-aminobutyric acid (GABA)A receptors in vivo in the brain using positron emission tomography (PET) imaging and 11C-flumazenil. Diazepam abolished tramadol-induced seizures, in contrast to naloxone, cyproheptadine and fexofenadine pretreatments. Despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05). No displacement of 11C-flumazenil brain kinetics was observed following tramadol administration in contrast to diazepam, suggesting that the observed interaction was not related to a competitive mechanism between tramadol and flumazenil at the benzodiazepine-binding site. Our findings do not support the involvement of serotoninergic, histaminergic, dopaminergic, norepinephrine or opioidergic pathways in tramadol-induced seizures in overdose, but they strongly suggest a tramadol-induced allosteric change of the benzodiazepine-binding site of GABAA receptors. Management of tramadol-poisoned patients should take into account that tramadol-induced seizures are mainly related to a GABAergic pathway.
Transferrin-Functionalized Liposomes for the Delivery of Gallic Acid: A Therapeutic Approach for Alzheimer’s Disease
Authors: Andrade Stéphanie , Loureiro Joana A. , Pereira Maria C.
Published: October 2022

Senile plaques composed of amyloid β (Aβ) fibrils are considered the leading cause of Alzheimer’s disease (AD). Molecules with the ability to inhibit Aβ aggregation and/or promote Aβ clearance are thus a promising approach for AD therapy. Our group recently demonstrated that gallic acid (GA) has strong anti-amyloidogenic properties. In this study, stealth liposomes were prepared for the delivery of GA for AD therapy. The liposomes were functionalized with transferrin (Tf) to direct them to the brain, since Tf receptors are overexpressed in the endothelial cells of the blood–brain barrier. GA-loaded Tf-functionalized liposomes showed mean diameters of 130 nm, low polydispersity index values, and neutral zeta potential. Moreover, the produced nanocarriers promoted the sustained release of GA over 5 days and are physically stable for 1 month under storage conditions. Furthermore, GA-loaded Tf-functionalized liposomes showed a strong ability to interact with Aβ1-42 monomers, slowing down the Aβ monomer-to-oligomer and oligomer-to-fibril transitions and decreasing the number of fibrils formed by 56%. In addition, the NPs disaggregated approximately 30% of preformed Aβ fibrils. The presented results suggest that Tf-functionalized liposomes could be a viable platform for the brain delivery of GA for AD therapy. Studies with animal models of AD will be valuable for validating the therapeutic efficacy of this novel liposomal formulation.
Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience
Authors: Amin Mohamadreza , Seynhaeve Ann L. B. , Sharifi Majid , Falahati Mojtaba , ten Hagen Timo L. M.
Published: October 2022

At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there.