bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics, Chemical Speciation and Health Risk Assessment of Heavy Metals in Paddy Soil and Rice around an Abandoned High-Arsenic Coal Mine Area, Southwest China
Authors: Liu Huijuan , Xie Jiao , Cheng Zhifei , Wu Xianliang
Published: May 2023

The concentrations of the heavy metals Pb, Cd, Cr, Hg, As, Cu and Zn in soil and locally produced grain (rice) were determined in paddy soil and rice around an abandoned high-arsenic coal mine area of Xingren county, southwest China. The health risk assessment was used to assess the multimedia and multipathway health risks of HM exposure in the study area. The results showed that the concentrations of As, Pb and Cd in soil were all higher than the corresponding limits for HMs in China. In terms of the accumulation and transfer capacity, Cd was more likely to transfer from the roots to rice, and its strong mobility may pose potential risks to local residents. The non-carcinogenic risks and carcinogenic risks of HM exposure in different media and exposure pathways were higher in children than adults. The total non-carcinogenic risks and carcinogenic risks in adults and children were higher than the standard limit values because of the HM exposure through ingesting rice husk. Among the exposure pathways evaluated, the contribution of diet was the largest, and As was the most important heavy metal in terms of the non-carcinogenic risk and carcinogenic risk factors. The total non-carcinogenic risks and carcinogenic risks caused by As in dietary crop (rice) accounted for 52% of the total in both adults and children. In order to maintain the health of residents in the study area, it is necessary to strictly strengthen the monitoring of heavy metal pollution in the study area and find effective soil improvement methods to reduce the health risks caused by heavy metal exposure.
Study of Dendromass Ashes Fusibility with the Addition of Magnesite, Limestone and Alumina
Authors: Vadász Pavol , Plešingerová Beatrice , Medveď Dávid , Sučik Gabriel , Bakajsová Radka , Petrov Vladimír
Published: May 2023

The fusibility of ash from woodchip combustion is characterised in the present work. The impact of the increase in MgO, CaO, and Al2O3 content in the bio-ash on the classification of ash into categories according to slagging and fouling indices was evaluated. The ash was characterized based on the chemical composition using slagging and fouling indices. However, these ash composition changes did not assign the ash into categories of the indices FU, SR, RS, and B/A (fouling, slagging, slag viscosity, basicity), with less ash inclination to slagging and fouling. The indices were primarily derived for ashes from coal combustion. The indices values characterizing the ash were compared with measured results of ash melting according to STN ISO 540. The measured ash fusibility values showed that the addition of magnesite, limestone, and alumina to dendro-ashes increases the DT (temperature of deformation), HT (temperature of hemisphere), and the AFI (ash fusibility index). There is no conformity between the values of the indices and the measurement of ash fusibility temperatures. In terms of temperatures in the combustion chamber, the measured sintering (Tsin) and DT are suitable for evaluating the tendency of ash to slagging and fouling as well as an accretion of ash particles sticking to the lining.
Acetogenins-Rich Fractions of Annona coriacea Suppress Human Glioblastoma Viability and Migration by Regulating Necroptosis and MMP-2 Activity In Vitro
Authors: Sousa Lorena R. , Oliveira Ana Gabriela S. , Arantes Antônio , Junqueira João Gabriel M. , Alexandre Gerso P. , Severino Vanessa G. P. , Reis Rui Manuel , Kim Bonglee , Ribeiro Rosy I. M. A.
Published: May 2023

Glioblastoma (GBM) is an incurable primary brain tumor with a poor prognosis. Resection, radiation therapy, and temozolomide (TMZ) are insufficient to increase survival, making the treatment limited. Thus, the search for more effective and specific treatments is essential, making plants a promising source for elucidating new anti-glioblastoma compounds. Accordingly, this study investigated the effects of four fractions of hexane and ethyl acetate extract of Annona coriacea Mart., enriched with acetogenins, against GBM cell lines. All four fractions were selectively cytotoxic to GBM cells when compared to TMZ. Moreover, A. coriacea fractions delayed cell migration; reduced cytoplasmic projections, the metalloproteinase 2 (MMP-2) activity; and induced morphological changes characteristic of necroptosis, possibly correlated with the increase in receptor-interacting protein kinase 1 and 3 (RIP-1 and RIP-3), apoptosis-inducing factor (AIF), and the non-activation of cleaved caspase 8. The present findings reinforce that fractions of A. coriacea Mart. should be considered for more studies focusing treatment of GBM.
Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome
Authors: Lei Dongyu , Yu Wenbo , Liu Yi , Jiang Yujie , Li Xiaohui , Lv Jing , Li Ying
Published: May 2023

TMAO is a new risk biomarker for cardiovascular disease. With trimethylammonium as its main chemical skeleton, TMAO is structurally similar to many endogenous metabolites, such as acetylcholine, carnitine, phosphorylcholine, etc. The mechanism of TMAO on the pathological process of CVD is still unclear. In this study, the quantitative analysis of plasma TMAO is conducted, and the contribution of Cathepsin B and NLRP3 inflammasome during the process of TMAO-induced endothelial injury was proposed and investigated at animal and cellular levels. Immunofluorescence assay was applied to represent the protein expression of Cathepsin B and NLRP3 inflammasome located at endothelial cells. The results showed that TMAO could disrupt endothelial cells permeability to induce endothelial injury, meanwhile, TMAO could increase NLRP3 inflammasome activation and promote the activity and expression of Cathepsin B in vitro and in vivo, whereas inhibition of NLRP3 inflammasome activation by MCC950 could protect the endothelial cells from TMAO associated endothelial injury via Cathepsin B. The study reveals that TMAO can cause endothelial injury via Cathepsin B-dependent NLRP3 inflammasome, and inhibition of Cathepsin B and NLRP3 inflammasome can reduce the TMAO-induced damage. The results provide new insight into the role of TMAO in CVD, which can be a potential therapeutic target for disease treatment and drug design.
Fatty Acids and Bilirubin as Intrinsic Autofluorescence Serum Biomarkers of Drug Action in a Rat Model of Liver Ischemia and Reperfusion
Authors: Croce Anna C. , Ferrigno Andrea , Palladini Giuseppina , Mannucci Barbara , Vairetti Mariapia , Di Pasqua Laura G.
Published: May 2023

The autofluorescence of specific fatty acids, retinoids, and bilirubin in crude serum can reflect changes in liver functional engagement in maintaining systemic metabolic homeostasis. The role of these fluorophores as intrinsic biomarkers of pharmacological actions has been investigated here in rats administered with obeticholic acid (OCA), a Farnesoid-X Receptor (FXR) agonist, proven to counteract the increase of serum bilirubin in hepatic ischemia/reperfusion (I/R) injury. Fluorescence spectroscopy has been applied to an assay serum collected from rats submitted to liver I/R (60/60 min ± OCA administration). The I/R group showed changes in the amplitude and profiles of emission spectra excited at 310 or 366 nm, indicating remarkable alterations in the retinoid and fluorescing fatty acid balance, with a particular increase in arachidonic acid. The I/R group also showed an increase in bilirubin AF, detected in the excitation spectra recorded at 570 nm. OCA greatly reversed the effects observed in the I/R group, confirmed by the biochemical analysis of bilirubin and fatty acids. These results are consistent with a relationship between OCA anti-inflammatory effects and the acknowledged roles of fatty acids as precursors of signaling agents mediating damaging responses to harmful stimuli, supporting serum autofluorescence analysis as a possible direct, real-time, cost-effective tool for pharmacological investigations.
Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions
Authors: Tarawneh Noor , Hamadneh Lama , Abu-Irmaileh Bashaer , Shraideh Ziad , Bustanji Yasser , Abdalla Shtaywy
Published: May 2023

Introduction: Berberine is a natural isoquinoline alkaloid with anti-cancer properties. Nevertheless, the underlying mechanism of its action in human colorectal cancer (CRC) has not been thoroughly elucidated. We investigated the anti-cancer effect of berberine on HT-29, SW-480 and HCT-116 human CRC cell lines. Methods: Cell proliferation, migration and invasion were studied by MTT assay, wound healing, transwell chambers and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunostaining were used to evaluate the expression of aquaporins (AQPs) 1, 3 and 5 in colon cancer cell lines before and after treatment with berberine (10, 30 and 100 µM). RT-qPCR and Western blotting were used to further explore the PI3K/AKT signaling pathway and the molecular mechanisms underlying berberine-induced inhibition of cell proliferation. Results: We demonstrated that treatment of these CRC cell lines with berberine inhibited cell proliferation, migration and invasion through induction of apoptosis and necrosis. HT-29, SW-480 and HCT-116 stained positively for AQP 1, 3 and 5, and berberine treatment down-regulated the expression of all three types of AQPs. Berberine also modulated PI3K/AKT pathway activity through up-regulating PTEN and down-regulating PI3K, AKT and p-AKT expression as well as suppressing its downstream targets, mTOR and p-mTOR at the protein level. Discussion/Conclusions: These findings indicate that berberine inhibited growth, migration and invasion of these colon cancer cell lines via down-regulation of AQP 1, 3 and 5 expressions, up-regulating PTEN which inhibited the PI3K/AKT pathway at the gene and protein levels, and that AQP 1, 3 and 5 expression level can be used as prognostic biomarkers for colon cancer metastasis.
In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS
Authors: Li Jing , Li Xinghua , Zhou Xiaohang , Yang Le , Sun Hui , Kong Ling , Yan Guangli , Han Ying , Wang Xijun
Published: May 2023

3,4,5,4’-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in ApcMin/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireXTM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model ApcMin/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the ApcMin/+ mice’s intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.
Characterization of the Key Compounds of Bell Pepper by Spectrophotometry and Gas Chromatography on the Effects of Induced Stress on the Concentration of Secondary Metabolite
Authors: Jimenez-García Sandra N. , Garcia-Mier Lina , Ramirez-Gomez Xóchitl S. , Guevara-Gonzalez Ramon G. , Aguirre-Becerra Humberto , Escobar-Ortiz Alexandro , Contreras-Medina Luis M. , Garcia-Trejo Juan F. , Vazquez-Cruz Moises A. , Feregrino-Perez Ana A.
Published: May 2023

Sweet peppers are consumed worldwide, and traditional uses have sparked interest in their applications as dietary antioxidants, which can be enhanced in plants using elicitors. These are endowed with phytochemicals with potential health benefits such as antioxidants, bioavailability, and bioaccessibility. The trend in metabolomics shows us chemical fingerprints linking metabolomics, innovative analytical form, and bioinformatics tools. The objective was to evaluate the impact of multiple stress interactions, elicitor concentrations, and electrical conductivity on the concentration of secondary metabolites to relate their response to metabolic pathways through the foliar application of a cocktail of said elicitors in pepper crops under greenhouse conditions. The extracts were analyzed by spectrophotometry and gas chromatography, and it was shown that the PCA analysis identified phenolic compounds and low molecular weight metabolites, confirming this as a metabolomic fingerprint in the hierarchical analysis. These compounds were also integrated by simultaneous gene and metabolite simulants to obtain effect information on different metabolic pathways. Showing changes in metabolite levels at T6 (36 mM H2O2 and 3.6 dS/m) and T7 (0.1 mM SA and 3.6 dS/m) but showing statistically significant changes at T5 (3.6 dS/m) and T8 (0.1 mM SA, 36 mM H2O2, and 3.6 dS/m) compared to T1 (32 dS/m) or control. Six pathways changed significantly (p < 0.05) in stress-induced treatments: aminoacyl t-RNA and valine-leucine-isoleucine biosynthesis, and alanine-aspartate-glutamate metabolism, glycoxylate-dicarboxylate cycle, arginine-proline, and citrate. This research provided a complete profile for the characterization of metabolomic fingerprint of bell pepper under multiple stress conditions.
New Chemistry of Chiral 1,3-Dioxolan-4-Ones
Authors: Aitken R. Alan , Power Lynn A. , Slawin Alexandra M. Z.
Published: May 2023

(2S,5S)-5-Phenyl-2-t-butyl-1,3-dioxolan-4-one, readily derived from mandelic acid, undergoes the Michael addition to butenolide and 4-methoxy-β-nitrostyrene with the absolute configuration of the products confirmed by X-ray diffraction in each case. In the former case, thermal fragmentation gives the phenyl ketone, thus illustrating use of the dioxolanone as a chiral benzoyl anion equivalent. The Diels–Alder cycloaddition chemistry of (2S)-5-methylene-2-t-butyl-1,3-dioxolan-4-one, derived from lactic acid, has been further examined with the X-ray structures of four adducts determined. In one case, thermal fragmentation of the adduct gives a chiral epoxy ketone resulting from the dioxolanone acting as a chiral ketene equivalent, while in others the products give insight into the mechanism of the dioxolanone fragmentation process.
Microwave-Assisted Synthesis of MoS2/BiVO4 Heterojunction for Photocatalytic Degradation of Tetracycline Hydrochloride
Authors: Cheng Cixin , Shi Qin , Zhu Weiwei , Zhang Yuheng , Su Wanyi , Lu Zizheng , Yan Jun , Chen Kao , Wang Qi , Li Junshan
Published: May 2023

Compared with traditional hydrothermal synthesis, microwave-assisted synthesis has the advantages of being faster and more energy efficient. In this work, the MoS2/BiVO4 heterojunction photocatalyst was synthesized by the microwave-assisted hydrothermal method within 30 min. The morphology, structure and chemical composition were characterized by X-ray diffraction (XRD), Raman, X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), and high-resolution transmission electron microscopy (HRTEM). The results of characterizations demonstrated that the synthesized MoS2/BiVO4 heterojunction was a spherical structure with dimensions in the nanorange. In addition, the photocatalytic activity of the samples was investigated by degrading tetracycline hydrochloride (TC) under visible light irradiation. Results indicated that the MoS2/BiVO4 heterojunction significantly improved the photocatalytic performance compared with BiVO4 and MoS2, in which the degradation rate of TC (5 mg L−1) by compound where the mass ratio of MoS2/BiVO4 was 5 wt% (MB5) was 93.7% in 90 min, which was 2.36 times of BiVO4. The active species capture experiments indicated that •OH, •O2− and h+ active species play a major role in the degradation of TC. The degradation mechanism and pathway of the photocatalysts were proposed through the analysis of the band structure and element valence state. Therefore, microwave technology provided a quick and efficient way to prepare MoS2/BiVO4 heterojunction photocatalytic efficiently.
Polygenic Risk Score, Lifestyles, and Type 2 Diabetes Risk: A Prospective Chinese Cohort Study
Authors: Liu Jia , Wang Lu , Cui Xuan , Shen Qian , Wu Dun , Yang Man , Dong Yunqiu , Liu Yongchao , Chen Hai , Yang Zhijie , Liu Yaqi , Zhu Meng , Ma Hongxia , Jin Guangfu , Qian Yun
Published: May 2023

The aim of this study was to generate a polygenic risk score (PRS) for type 2 diabetes (T2D) and test whether it could be used in identifying high-risk individuals for lifestyle intervention in a Chinese cohort. We genotyped 80 genetic variants among 5024 participants without non-communicable diseases at baseline in the Wuxi Non-Communicable Diseases cohort (Wuxi NCDs cohort). During the follow-up period of 14 years, 440 cases of T2D were newly diagnosed. Using Cox regression, we found that the PRS of 46 SNPs identified by the East Asians was relevant to the future T2D. Participants with a high PRS (top quintile) had a two-fold higher risk of T2D than the bottom quintile (hazard ratio: 2.06, 95% confidence interval: 1.42–2.97). Lifestyle factors were considered, including cigarette smoking, alcohol consumption, physical exercise, diet, body mass index (BMI), and waist circumference (WC). Among high-PRS individuals, the 10-year incidence of T2D slumped from 6.77% to 3.28% for participants having ideal lifestyles (4–6 healthy lifestyle factors) compared with poor lifestyles (0-2 healthy lifestyle factors). When integrating the high PRS, the 10-year T2D risk of low-clinical-risk individuals exceeded that of high-clinical-risk individuals with a low PRS (3.34% vs. 2.91%). These findings suggest that the PRS of 46 SNPs could be used in identifying high-risk individuals and improve the risk stratification defined by traditional clinical risk factors for T2D. Healthy lifestyles can reduce the risk of a high PRS, which indicates the potential utility in early screening and precise prevention.
Comparison of Several Adiposity Indexes in Predicting Hypertension among Chinese Adults: Data from China Nutrition and Health Surveillance (2015–2017)
Authors: Li Yuge , Yu Dongmei , Yang Yuxiang , Cheng Xue , Piao Wei , Guo Qiya , Xu Xiaoli , Zhao Liyun , Wang Yuying
Published: May 2023

The current study is to explore the association of the Chinese visceral adiposity index (CVAI) with hypertension, and to compare the predictive power of different adiposity indexes regarding hypertension among Chinese adults aged over 45 years. A total of 99,201 participants aged over 45 years from the China Nutrition and Health Surveillance 2015–2017 were included in this study. Multivariate adjusted logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of hypertension. Multivariate adjusted restricted cubic spline analyses were applied to explore the association of adiposity indexes with hypertension. Receiver operating characteristic (ROC) analyses were used to compare the predictive powers of different adiposity indexes of hypertension. All eight adiposity indexes included in this study were positively associated with hypertension. Compared with those in the lowest quartile of the CVAI, the participants in the highest quartile showed a significantly higher risk of hypertension (OR = 3.70, 95% CI = 3.54–3.86) after multiple adjustments. The ROC analyses suggested that the CVAI was the strongest predictor of hypertension compared to other adiposity indexes in both genders. The findings supported that the CVAI could serve as a reliable and cost-effective method for early identifying hypertension risk.
Impact of Final Phase Social Isolation and the COVID-19 Pandemic on Eating Behavior, Sleep Quality, and Anxiety Level
Authors: do Carmo Simone Gonzaga , Oliveira Júlia Paulino Teixeira , Aragão Bruna de Almeida , Botelho Patrícia Borges
Published: May 2023

The coronavirus disease 2019 (COVID-19) pandemic has resulted in economic, social, and behavioral changes in people, which may favor several long-term consequences. This study evaluated the effects of the COVID-19 pandemic on eating behavior and mental health in the final phase of social isolation. This cross-sectional study included 756 adults that completed an online questionnaire. Individuals were stratified into those who had been infected with COVID-19 (GCOV) and those who did not (GNCOV). The GCOV group had higher weight (p = 0.013), body mass index (BMI) (p = 0.005), anxiety levels (p = 0.040), sleep disorders (p = 0.009), and poorer sleep quality (p = 0.0028). In the GCOV, the consumption of ultra-processed foods was associated with higher anxiety levels and poorer sleep quality. A higher proportion of individuals who consumed more than five servings of in natura food was observed in the group with taste and olfactory dysfunction than in the group without. Obesity contributes to uncontrolled and emotional eating disorders, increased anxiety, and worsened sleep. Therefore, COVID-19 impaired mental health and eating behavior even in the long term. These changes were potentiated by the presence of obesity and consumption of ultra-processed foods, evidencing the importance of monitoring these individuals even after the resolution of COVID-19.
The Effects of the Mediterranean Diet on Health and Gut Microbiota
Authors: Barber Thomas M. , Kabisch Stefan , Pfeiffer Andreas F. H. , Weickert Martin O.
Published: May 2023

The Mediterranean Diet (MD) is plant-based and consists of multiple daily portions of vegetables, fruit, cereals, and olive oil. Although there are challenges with isolating the MD from the typical Mediterranean lifestyle and culture (including prolonged ‘social’ meals and siestas), much evidence supports the health benefits of the MD that include improved longevity, reduced metabolic risk of Diabetes Mellitus, obesity, and Metabolic Syndrome, reduced risk of malignancy and cardiovascular disease, and improved cognitive function. The MD is also associated with characteristic modifications to gut microbiota, mediated through its constituent parts (primarily dietary fibres, extra virgin olive oil, and polyunsaturated fatty acids [including ω-3]). These include enhanced growth of species that produce short-chain fatty acids (butyrate), such as Clostridium leptum and Eubacterium rectale, enhanced growth of Bifidobacteria, Bacteroides, and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes in gut microbiota are known to be associated favourably with inflammatory and oxidative status, propensity for malignancy and overall metabolic health. A key challenge for the future is to explore the extent to which the health benefits of the MD are mediated by such changes to gut microbiota. The MD confers both health and environmental benefits. Adoption of the MD should perhaps be encouraged and facilitated more generally and not just restricted to populations from Mediterranean regions. However, there are key challenges to this approach that include limited perennial availability of the constituent parts of the MD in some non-Mediterranean regions, intolerability of a high-fibre diet for some people, and potential cultural disconnects that juxtapose some traditional (including Western) diets with the MD.
Comparison of Clinical, Biochemical and Histological Features between Adult Celiac Patients with High and Low Anti-Transglutaminase IgA Titer at Diagnosis and Follow-Up
Authors: Galli Gloria , Carabotti Marilia , Conti Laura , Scalamonti Silvia , Annibale Bruno , Lahner Edith
Published: May 2023

In adults, celiac disease (CD) diagnosis is based on specific serology (anti-transglutaminase IgA-anti-tTG) and duodenal histology. Evidence is raising the possibility of perform CD diagnosis based only on high anti-tTG titer in children. We aimed to evaluate clinical, histological and biochemical differences between adult patients with high tTG IgA titer (HT) and those with low titer (LT) at CD diagnosis and follow-up. This retrospective study included consecutive adult CD patients divided into two groups: HT (anti-tTG > 10 × ULN) and LT (anti-tTG < 10 × ULN). Clinical, biochemical and histological features were compared between groups at CD diagnosis and at follow-up. A total of 291 patients were included (HT: 47.1%; LT: 52.9%). At CD diagnosis, HT patients showed a non ‘classical’ presentation (p = 0.04), Marsh 3C (p = 0.005), hypoferritinaemia (p = 0.006) and osteopenia/osteoporosis (p = 0.04) more frequently than LT patients. A total of 216 patients (HT: 48.6%; LT: 51.4%) performed a follow-up after a median Gluten-free diet of 14 months; HT patients had persistent antibodies positivity (p = 0.001) more frequently and GI symptoms (p = 0.04) less frequently than LT patients. In conclusion, HT patients presented severe histological damage more frequently at diagnosis, recovering similarly to LT patients after the start of the Gluten-free diet. At follow-up, anti-tTG persisted positive in HT more frequently compared to LT patients, without differences regarding histological recovery and clinical improvement.
The Short-Term Variation of Human Gut Mycobiome in Response to Dietary Intervention of Different Macronutrient Distributions
Authors: Tian Yunyi , Gou Wanglong , Ma Yue , Shuai Menglei , Liang Xinxiu , Fu Yuanqing , Zheng Ju-Sheng
Published: May 2023

While the human gut is home to a complex and diverse community of microbes, including bacteria and fungi, research on the gut microbiome has largely focused on bacteria, with relatively little attention given to the gut mycobiome. This study aims to investigate how diets with different dietary macronutrient distributions impact the gut mycobiome. We investigated gut mycobiome response to high-carbohydrate, low-fat (HC) and low-carbohydrate high-fat (LC) diet interventions based on a series of 72-day feeding-based n-of-1 clinical trials. A total of 30 participants were enrolled and underwent three sets of HC and LC dietary interventions in a randomized sequence. Each set lasted for 24 days with a 6-day washout period between dietary interventions. We collected and analyzed the fungal composition of 317 stool samples before and after each intervention period. To account for intra-individual variation across the three sets, we averaged the mycobiome data from the repeated sets for analysis. Of the 30 participants, 28 (aged 22–34 years) completed the entire intervention. Our results revealed a significant increase in gut fungal alpha diversity (p < 0.05) and significant changes in fungal composition (beta diversity, p < 0.05) after the HC dietary intervention. Specifically, we observed the enrichment of five fungal genera (Pleurotus, Kazachstania, Auricularia, Paraphaeosphaeria, Ustilaginaceae sp.; FDR < 0.052) and depletion of one fungal genus (Blumeria; FDR = 0.03) after the HC intervention. After the LC dietary intervention, one fungal genus was enriched (Ustilaginaceae sp.; FDR = 0.003), and five fungal genera were depleted (Blumeria, Agaricomycetes spp., Malassezia, Rhizopus, and Penicillium; FDR < 0.1). This study provides novel evidence on how the gut mycobiome structure and composition change in response to the HC and LC dietary interventions and reveals diet-specific changes in the fungal genera.
Branched-Chain Amino Acids Metabolism and Their Roles in Retinopathy: From Relevance to Mechanism
Authors: Zhang Xiaonan , Xia Mengxue , Wu Yingjie , Zhang Fang
Published: May 2023

Retinopathy is one of the leading causes of irreversible blindness and vision loss worldwide. Imbalanced nutrients play important roles in the pathogenesis and pathophysiology of retinal diseases. Branched-Chain Amino Acids (BCAAs), as essential amino acids, perform a variety of biological functions, including protein synthesis, glucose metabolism, lipid metabolism, inflammation, and oxidative stress in metabolic tissues of diabetes and aging-related diseases. Recently, it has been shown that BCAAs are highly related to neuroprotection, oxidative stress, inflammatory and glutamate toxicity in the retina of retinopathy. Therefore, this review summarizes the alterations of BCAA levels in retinopathy, especially diabetic retinopathy and aging-related macular disease, and the genetics, functions, and mechanisms of BCAAs in the retina as well as other metabolic tissues for reference. All of these efforts aim to provide fundamental knowledge of BCAAs for further discoveries and research on retina health based on the sensing and signaling of essential amino acids.
Association of Eating Pattern, Chronotype, and Social Jetlag: A Cross-Sectional Study Using Data Accumulated in a Japanese Food-Logging Mobile Health Application
Authors: Nitta Lyie , Tahara Yu , Shinto Takae , Makino Saneyuki , Kuwahara Mai , Tada Ayako , Abe Nanako , Michie Mikiko , Shibata Shigenobu
Published: May 2023

Chronotype (morningness–eveningness) and social jetlag (SJL; discrepancy in the sleep pattern between the weekday and weekend) are related to eating behavior and health. The association between sleep behavior and the daily macro- and micronutrient eating pattern of each meal (breakfast, lunch, and dinner) have not been discussed well and need more evidence. Here, meal pattern datasets of Japanese participants aged 20–59 years were obtained as averages over 1 month from the data stored in the food-logging app “Asken”. We allocated three groups for each chronotype and SJL. Multiple regression analyses revealed that morning chronotype and small SJL were associated with higher total daily intake of potassium, fiber, magnesium, phosphorus, and vitamin K. Breakfast energy intake and consumption of nutrients, including protein, lipid, carbohydrate, and minerals, were higher in the morning chronotype or small SJL. Lunch intake of potassium, cholesterol, fiber, magnesium, and vitamin K was also higher in the morning chronotype or small SJL. Dinner energy intake and nutrient intake of proteins, lipids, carbohydrates, sodium, and saturated fatty acids were lower in the morning chronotype or small SJL. The current data would help to establish a detailed reference for dietary intake which considers eating patterns over a day.
Ultra-Processed Food Intakes Are Associated with Depression in the General Population: The Korea National Health and Nutrition Examination Survey
Authors: Lee Sunghee , Choi Myungjin
Published: May 2023

Depression is the most common mental illnesses worldwide. The consumption of ultra-processed food (UPF) has increased globally due to its affordability and convenience; however, only a few studies have investigated the link between UPF intake and depression in the general population. We investigated the associations between UPF and depression using the Korea National Health and Nutrition Examination Survey. A total of 9463 individuals (4200 males and 5263 females) aged above 19 years old participated in this study. The prevalence of depression was identified using the Patient Health Questionnaire-9. Dietary intake was assessed through a 24-h recall interview. The percentage of energy from UPFs was ascertained based on the NOVA classification. The associations between the quartile ranges of UPF intake and depression were estimated using logistic regression models. Individuals in the highest quartile had a 1.40 times higher likelihood of having depression, with marginal significance (95% confidence intervals (CIs) = 1.00–1.96). In a sex-specific stratification, only females demonstrated a significant association (odds ratio (OR) = 1.51, 95% CI 1.04–2.21), even after adjusting for confounders (p-value for trend = 0.023). Our findings revealed a significant association between higher UPF intake and depression among females but not among males in the Korean general population.
Adansonia digitata L. (Baobab) Bioactive Compounds, Biological Activities, and the Potential Effect on Glycemia: A Narrative Review
Authors: Silva Maria Leonor , Rita Keyla , Bernardo Maria Alexandra , Mesquita Maria Fernanda de , Pintão Ana Maria , Moncada Margarida
Published: May 2023

Adansonia digitata L. fruit, also known as baobab, has been used traditionally throughout the world for its medicinal properties. Ethnopharmacological uses of various plant parts have been reported for hydration, antipyretic, antiparasitic, antitussive, and sudorific properties and also in the treatment of diarrhea and dysentery in many African countries. Several studies have revealed that in addition to these applications, baobab has antioxidant, anti-inflammatory, analgesic, and antimicrobial activities. The health benefits of baobab have been attributed to its bioactive compounds, namely phenols, flavonoids, proanthocyanins, tannins, catechins, and carotenoids. Baobab fruit is also an important source of vitamin C and micronutrients, including zinc, potassium, magnesium, iron, calcium, and protein, which may reduce nutritional deficiencies. Despite scientific studies revealing that this fruit has a wide diversity of bioactive compounds with beneficial effects on health, there is a gap in the review of information about their mechanisms of action and critical analysis of clinical trials exploring, in particular, their effect on glycemia regulation. This work aims to present a current overview of the bioactive compounds, biological activities, and effects of A. digitata fruit on blood glucose, highlighting their potential mechanisms of action and effects on glycemia regulation, evaluated in recent animal and human trials.
The STAT3-Regulated Autophagy Pathway in Glioblastoma
Authors: Laribee Ronald Nicholas , Boucher Andrew B. , Madireddy Saivikram , Pfeffer Lawrence M.
Published: May 2023

Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.
Identifying Crude Drugs in Kampo Medicines Associated with Drug-Induced Liver Injury Using the Japanese Adverse Drug Event Report Database: A Comprehensive Survey
Authors: Kimura Kyosuke , Kikegawa Mami , Kan Yusuke , Uesawa Yoshihiro
Published: May 2023

The current study aimed to identify the crude drugs associated with drug-induced liver injury (DILI) in 148 Kampo medicines prescribed throughout Japan using the Japanese Adverse Drug Event Report (JADER) database, a large-scale spontaneous reporting system in Japan. First, we tabulated the number of DILI reports from the report-based dataset and the background information from the patient-based dataset. Thereafter, we combined the 126 crude drugs into 104 crude drug groups to examine multicollinearity. Finally, the reporting odds ratios (RORs), 95% confidence intervals, p values for Fisher’s exact test, and number of reports were calculated for each crude group to identify those associated with DILI. Notably, the number of adverse event reports for DILI (63,955) exceeded that for interstitial lung disease (51,347), the most common adverse event. In total, 78 crude drug groups (90 crude drugs) were reported to have an ROR > 1, a p < 0.05, and ≥10 reported cases. Our results highlight DILI as an essential issue, given that it was among the most frequently reported adverse drug reactions. We were able to clearly identify the crude drugs associated with DILI, which could help manage adverse drug reactions attributed to Kampo medicines and crude drugs.
New Organometallic Ru(II) Compounds with Lonidamine Motif as Antitumor Agents
Authors: Shutkov Ilya A. , Okulova Yulia N. , Mazur Dmitrii M. , Melnichuk Nikolai A. , Babkov Denis A. , Sokolova Elena V. , Spasov Alexander A. , Milaeva Elena R. , Nazarov Alexey A.
Published: May 2023

The combination of one molecule of organic and metal-based fragments that exhibit antitumor activity is a modern approach in the search for new promising drugs. In this work, biologically active ligands based on lonidamine (a selective inhibitor of aerobic glycolysis used in clinical practice) were introduced into the structure of an antitumor organometallic ruthenium scaffold. Resistant to ligand exchange reactions, compounds were prepared by replacing labile ligands with stable ones. Moreover, cationic complexes containing two lonidamine-based ligands were obtained. Antiproliferative activity was studied in vitro by MTT assays. It was shown that the increase in the stability in ligand exchange reactions does not influence cytotoxicity. At the same time, the introduction of the second lonidamine fragment approximately doubles the cytotoxicity of studied complexes. The ability to induce apoptosis and caspase activation in tumour cell MCF7 was studied by employing flow cytometry.
The Mineralocorticoid Receptor on Smooth Muscle Cells Promotes Tacrolimus-Induced Renal Injury in Mice
Authors: Figueroa Stefanny M. , Bertocchio Jean-Philippe , Nakamura Toshifumi , El-Moghrabi Soumaya , Jaisser Frédéric , Amador Cristián A.
Published: May 2023

Tacrolimus (Tac) is a calcineurin inhibitor commonly used as an immunosuppressor after solid organ transplantation. However, Tac may induce hypertension, nephrotoxicity, and an increase in aldosterone levels. The activation of the mineralocorticoid receptor (MR) is related to the proinflammatory status at the renal level. It modulates the vasoactive response as they are expressed on vascular smooth muscle cells (SMC). In this study, we investigated whether MR is involved in the renal damage generated by Tac and if the MR expressed in SMC is involved. Littermate control mice and mice with targeted deletion of the MR in SMC (SMC-MR-KO) were administered Tac (10 mg/Kg/d) for 10 days. Tac increased the blood pressure, plasma creatinine, expression of the renal induction of the interleukin (IL)-6 mRNA, and expression of neutrophil gelatinase-associated lipocalin (NGAL) protein, a marker of tubular damage (p < 0.05). Our study revealed that co-administration of spironolactone, an MR antagonist, or the absence of MR in SMC-MR-KO mice mitigated most of the unwanted effects of Tac. These results enhance our understanding of the involvement of MR in SMC during the adverse reactions of Tac treatment. Our findings provided an opportunity to design future studies considering the MR antagonism in transplanted subjects.
Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy
Authors: Funeh Cyprine Neba , Bridoux Jessica , Ertveldt Thomas , De Groof Timo W. M. , Chigoho Dora Mugoli , Asiabi Parinaz , Covens Peter , D’Huyvetter Matthias , Devoogdt Nick
Published: May 2023

The precise delivery of cytotoxic radiation to cancer cells through the combination of a specific targeting vector with a radionuclide for targeted radionuclide therapy (TRT) has proven valuable for cancer care. TRT is increasingly being considered a relevant treatment method in fighting micro-metastases in the case of relapsed and disseminated disease. While antibodies were the first vectors applied in TRT, increasing research data has cited antibody fragments and peptides with superior properties and thus a growing interest in application. As further studies are completed and the need for novel radiopharmaceuticals nurtures, rigorous considerations in the design, laboratory analysis, pre-clinical evaluation, and clinical translation must be considered to ensure improved safety and effectiveness. Here, we assess the status and recent development of biological-based radiopharmaceuticals, with a focus on peptides and antibody fragments. Challenges in radiopharmaceutical design range from target selection, vector design, choice of radionuclides and associated radiochemistry. Dosimetry estimation, and the assessment of mechanisms to increase tumor uptake while reducing off-target exposure are discussed.
Anisotropic, Hydrogel Microparticles as pH-Responsive Drug Carriers for Oral Administration of 5-FU
Authors: Teora Serena P. , Panavaité Elada , Sun Mingchen , Kiffen Bas , Wilson Daniela A.
Published: May 2023

In the last 20 years, the development of stimuli-responsive drug delivery systems (DDS) has received great attention. Hydrogel microparticles represent one of the candidates with the most potential. However, if the role of the cross-linking method, polymer composition, and concentration on their performance as DDS has been well-studied, still, a lot needs to be explained regarding the effect caused by the morphology. To investigate this, herein, we report the fabrication of PEGDA–ALMA-based microgels with spherical and asymmetric shapes for 5-fluorouracil (5-FU) on-demand loading and in vitro pH-triggered release. Due to anisotropic properties, the asymmetric particles showed an increased drug adsorption and higher pH responsiveness, which in turn led to a higher desorption efficacy at the target pH environment, making them an ideal candidate for oral administration of 5-FU in colorectal cancer. The cytotoxicity of empty spherical microgels was higher than the cytotoxicity of empty asymmetric microgels, suggesting that the gel network’s mechanical proprieties of anisotropic particles were a better three-dimensional environment for the vital functions of cells. Upon treatment with drug-loaded microgels, the HeLa cells’ viability was lower after incubation with asymmetric particles, confirming a minor release of 5-FU from spherical particles.
Isolation of Secondary Metabolites from Achillea grandifolia Friv. (Asteraceae) and Main Compounds’ Effects on a Glioblastoma Cellular Model
Authors: Tsiftsoglou Olga S. , Krigas Nikos , Gounaris Christos , Papitsa Christina , Nanouli Maria , Vartholomatos Evrysthenis , Markopoulos Georgios S. , Isyhou Rafaela , Alexiou George , Lazari Diamanto
Published: May 2023

This study aims at the isolation and structural determination of the secondary metabolites of the herbaceous perennial plant Achillea grandifolia Friv. (Asteraceae). The examination of the non-volatile content of the leaves and flowers of A. grandifolia afforded the isolation of sixteen secondary metabolites. On the basis of NMR spectra, the identified compounds included ten sesquiterpene lactones; three guaianolides—rupicolin A (1), rupicolin B (2), and (4S,6aS,9R,9aS,9bS)-4,6a,9-trihydroxy-9-methyl-3,6-dimethylene-3a,4,5,6,6a,9,9a,9b-octahydro-3H-azuleno [4,5-b]furan-2-one (3); two eudesmanolides—artecalin (4) and ridentin B (5); two sesquiterpene methyl esters—(1S,2S,4αR,5R,8R,8αS)-decahydro-1,5,8-trihydroxy-4α,8-dimethyl–methylene-2-naphthaleneacetic acid methylester (6) and 1β, 3β, 6α-trihydroxycostic acid methyl ester (7); three secoguaianolides—acrifolide (8), arteludovicinolide A (9), and lingustolide A (10); and an iridoid—loliolide (11). Moreover, five known flavonoids, i.e., apigenin, luteolin, eupatolitin, apigenin 7-O-glucoside, and luteolin 7-O-glucoside (12-16) were also purified from the aerial parts of the plant material. We also investigated the effect of rupicolin A (1) and B (2) (main compounds) on U87MG and T98G glioblastoma cell lines. An MTT assay was performed to define cytotoxic effects and to calculate the IC50, while flow cytometry was employed to analyze the cell cycle. The IC50 values of reduced viability during the 48 h treatment for compound (1) and (2) were 38 μM and 64 μM for the U87MG cells and 15 μM and 26 μM for the T98G cells, respectively. Both rupicolin A and B induced a G2/M cell cycle arrest.
Germanium Dioxide Nanoparticles Mitigate Biochemical and Molecular Changes Characterizing Alzheimer’s Disease in Rats
Authors: Abdel Gaber Sara A. , Hamza Amal H. , Tantawy Mohamed A. , Toraih Eman A. , Ahmed Hanaa H.
Published: May 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder that jeopardizes the lives of diagnosed patients at late stages. This study aimed to assess, for the first time, the efficiency of germanium dioxide nanoparticles (GeO2NPs) in mitigating AD at the in vivo level compared to cerium dioxide nanoparticles (CeO2NPs). Nanoparticles were synthesized using the co-precipitation method. Their antioxidant activity was tested. For the bio-assessment, rats were randomly assigned into four groups: AD + GeO2NPs, AD + CeO2NPs, AD, and control. Serum and brain tau protein, phosphorylated tau, neurogranin, amyloid β peptide 1-42, acetylcholinesterase, and monoamine oxidase levels were measured. Brain histopathological evaluation was conducted. Furthermore, nine AD-related microRNAs were quantified. Nanoparticles were spherical with diameters ranging from 12–27 nm. GeO2NPs exhibited a stronger antioxidant activity than CeO2NPs. Serum and tissue analyses revealed the regression of AD biomarkers to almost control values upon treatment using GeO2NPs. Histopathological observations strongly supported the biochemical outcomes. Then, miR-29a-3p was down-regulated in the GeO2NPs-treated group. This pre-clinical study substantiated the scientific evidence favoring the pharmacological application of GeO2NPs and CeO2NPs in AD treatment. Our study is the first report on the efficiency of GeO2NPs in managing AD. Further studies are needed to fully understand their mechanism of action.
One Step Purification—Vaccine Delivery System
Authors: Soto Ernesto R. , Specht Charles A. , Lee Chrono K. , Levitz Stuart M. , Ostroff Gary R.
Published: May 2023

Glucan particles (GPs) are hollow, porous 3–5 µm microspheres derived from the cell walls of Baker’s yeast (Saccharomyces cerevisiae). Their 1,3-β-glucan outer shell allows for receptor-mediated uptake by macrophages and other phagocytic innate immune cells expressing β-glucan receptors. GPs have been used for the targeted delivery of a wide range of payloads, including vaccines and nanoparticles, encapsulated inside the hollow cavity of GPs. In this paper, we describe the methods to prepare GP-encapsulated nickel nanoparticles (GP-Ni) for the binding of histidine (His)-tagged proteins. His-tagged Cda2 cryptococcal antigens were used as payloads to demonstrate the efficacy of this new GP vaccine encapsulation approach. The GP-Ni-Cda2 vaccine was shown to be comparable to our previous approach utilizing mouse serum albumin (MSA) and yeast RNA trapping of Cda2 in GPs in a mouse infection model. This novel GP-Ni approach allows for the one-step binding of His-tagged vaccine antigens and encapsulation in an effective delivery vehicle to target vaccines to antigen-presenting cells (APCs), antigen discovery, and vaccine development.