bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-4732-3p Is Dysregulated in Breast Cancer Patients with Cardiotoxicity, and Its Therapeutic Delivery Protects the Heart from Doxorubicin-Induced Oxidative Stress in Rats
Authors: Sánchez-Sánchez Rafael , Reinal Ignacio , Peiró-Molina Esteban , Buigues Marc , Tejedor Sandra , Hernándiz Amparo , Selva Marta , Hervás David , Cañada Antonio J. , Dorronsoro Akaitz , Santaballa Ana , Salvador Carmen , Caiment Florian , Kleinjans Jos , Martínez-Dolz Luis , Moscoso Isabel , Lage Ricardo , González-Juanatey José R. , Panadero Joaquín , Aparicio-Puerta Ernesto , Bernad Antonio , Sepúlveda Pilar
Published: October 2022

Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest). MiR-4732-3p was the only microRNA identified in all regression models and was downregulated in patients that experienced cardiotoxicity. MiR-4732-3p was also present in neonatal rat cardiomyocytes and cardiac fibroblasts and was modulated by anthracycline treatment. A miR-4732-3p mimic was cardioprotective in cardiac and fibroblast cultures, following doxorubicin challenge, in terms of cell viability and ROS levels. Notably, administration of the miR-4732-3p mimic in doxorubicin-treated rats preserved cardiac function, normalized weight loss, induced angiogenesis, and decreased apoptosis, interstitial fibrosis and cardiac myofibroblasts. At the molecular level, miR-4732-3p regulated genes of TGFβ and Hippo signaling pathways. Overall, the results indicate that miR-4732-3p is a novel biomarker of cardiotoxicity that has therapeutic potential against anthracycline-induced heart damage.
Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease
Authors: Higashi Yukihito
Published: October 2022

Oxidative stress and chronic inflammation play an important role in the pathogenesis of atherosclerosis. Atherosclerosis develops as the first step of vascular endothelial dysfunction induced by complex molecular mechanisms. Vascular endothelial dysfunction leads to oxidative stress and inflammation of vessel walls, which in turn enhances vascular endothelial dysfunction. Vascular endothelial dysfunction and vascular wall oxidative stress and chronic inflammation make a vicious cycle that leads to the development of atherosclerosis. Simultaneously capturing and accurately evaluating the association of vascular endothelial function with oxidative stress and inflammation would be useful for elucidating the pathophysiology of atherosclerosis, determining treatment efficacy, and predicting future cardiovascular complications. Intervention in both areas is expected to inhibit the progression of atherosclerosis and prevent cardiovascular complications.
Glutathione–Hemin/Hematin Adduct Formation to Disintegrate Cytotoxic Oxidant Hemin/Hematin in Human K562 Cells and Red Blood Cells’ Hemolysates: Impact of Glutathione on the Hemolytic Disorders and Homeostasis
Authors: Georgiou-Siafis Sofia K. , Samiotaki Martina K. , Demopoulos Vassilis J. , Panayotou George , Tsiftsoglou Asterios S.
Published: October 2022

Hemin, an oxidized form of heme, acts as potent oxidant to regulate glutathione (GSH) content in pro-erythroid K562 nucleated cells, via activation of the KEAP1/NRF2 defensive signaling pathway. Moreover, GSH, as an essential metabolite, is involved in the regulation of cell-redox homeostasis and proposed to scavenge cytotoxic free heme, which is released from hemoglobin of damaged red blood cells (RBCs) during different hemolytic disorders. In the present study, we aimed to uncover the molecular mechanism by which GSH inhibits hemin-induced cytotoxicity (HIC) by affecting hemin’s structural integrity in K562 cells and in RBC hemolysates. GSH, along with other thiols (cysteine, thioglycolic acid, and mercaptoethanol) altered the spectrum of hemin, while each of them co-added with hemin in cultures of K562 cells prevented HIC and growth arrest and markedly reduced the intracellular level of hemin. In addition, GSH endogenous levels served as a barrier to HIC in K562 cells, as shown by the depletion in GSH. LC-MS/MS analysis of the in vitro reaction between hemin and GSH revealed at least five different isomers of GSH–hemin adducts, as well as hydroxy derivatives as reaction products, which are characterized by unique mass spectra (MS). The latter allowed the detection of adducts in human RBC hemolysates. Based on these findings, we proposed a molecular mechanism via which GSH prevents HIC and structurally disintegrates heme. An analogous reaction was observed in RBC hemolysates via direct inter-reaction between hematin (ferric and hydroxide heme) released from hemoglobin and GSH. Overall, GSH–hematin adducts could be considered as novel entities of the human metabolome of RBCs in hemolytic disorders.
Optimization of Supercritical Carbon Dioxide Extraction of Saussurea costus Oil and Its Antimicrobial, Antioxidant, and Anticancer Activities
Authors: Ahmed Hanaa Y. , Kareem Sayed M. , Atef Ahmed , Safwat Nesreen A. , Shehata Reda M. , Yosri Mohammed , Youssef Mahmoud , Baakdah Morooj M. , Sami Rokayya , Baty Roua S. , Alsubhi Nouf H. , Alrefaei Ghadeer I. , Shati Ali A. , Elsaid Fahmy G.
Published: October 2022

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils’ anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 μg/mL, respectively. In contrast, at 20 MPa, the IC50 values were about 2.33, 6.59, and 19.0 μg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 μg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC50 14.4 μg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens.
Relationship between Phenolic Compounds and Antioxidant Activity in Berries and Leaves of Raspberry Genotypes and Their Genotyping by SSR Markers
Authors: Lebedev Vadim G. , Lebedeva Tatyana N. , Vidyagina Elena O. , Sorokopudov Vladimir N. , Popova Anna A. , Shestibratov Konstantin A.
Published: October 2022

The red raspberry is one of the world’s most popular berries. The main direction of its breeding has switched to nutritional quality, and the evaluation of raspberry germplasm for antioxidant content and activity is very important. As berries, raspberry leaves contain valuable bioactive compounds, but the optimal time for their collection is unknown. We evaluated 25 new breeding lines and standard raspberry cultivars for their polyphenolic content and antioxidant capacity. The antioxidant activity of berries correlated better with the content of total phenolics (0.88 and 0.92) and flavonoids (0.76 and 0.88) than with anthocyanins (0.37 and 0.66). Two breeding lines were significantly superior to the standard cultivars and can be used in further breeding. Leaves collected in three phenological phases of the raspberry contained more phenolics (5.4-fold) and flavonoids (4.1-fold) and showed higher antioxidant activities (2.4-fold in FRAP assay, 2.2-fold in ABTS) than berries. The optimal time for harvesting raspberry leaves is the fruit ripening stage, with exceptions for some cultivars. Genetic diversity analysis using microsatellite (SSR) markers from flavonoid biosynthesis genes divided the genotypes into five clusters, generally in agreement with their kinships. The relationship between genetic data based on metabolism-specific SSR markers and the chemical diversity of cultivars was first assessed. The biochemical and genetic results show a strong correlation (0.78). This study is useful for further the improvement of raspberry and other berry crops.
Impact of Phenol-Enriched Olive Oils on Serum Metabonome and Its Relationship with Cardiometabolic Parameters: A Randomized, Double-Blind, Cross-Over, Controlled Trial
Authors: Farràs Marta , Swann Jonathan Richard , Rowland Ian , Rubió Laura , Subirana Isaac , Catalán Úrsula , Motilva Maria José , Solà Rosa , Covas Maria Isabel , Blanco-Vaca Francisco , Fitó Montserrat , Mayneris-Perxachs Jordi
Published: October 2022

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum 1H-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases.
Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Application in Cancer Therapy
Authors: Chen Wanwen , Cheng Hao , Xia Wenshui
Published: October 2022

As an essential micronutrient, selenium participates in numerous life processes and plays a key role in human health. In the past decade, selenium nanoparticles (SeNPs) have attracted great attention due to their excellent functionality for potential applications in pharmaceuticals. However, the utilization of SeNPs has been restricted by their instability and low targeting ability. Since the existing reviews mainly focused on the applications of SeNPs, this review highlights the synthesis of SeNPs and the strategies to improve their stability and targeting ability through surface functionalization. In addition, the utilization of functionalized SeNPs for the single and co-delivery of drugs or genes to achieve the combination of therapy are also presented, with the emphasis on the potential mechanism. The current challenges and prospects of functionalized SeNPs are also summarized. This review may provide valuable information for the design of novel functionalized SeNPs and promote their future application in cancer therapy.
Role of NADPH Oxidases in Blood–Brain Barrier Disruption and Ischemic Stroke
Authors: Hernandes Marina S. , Xu Qian , Griendling Kathy K.
Published: October 2022

NADPH oxidases (Nox) are one of the main sources of reactive oxygen species (ROS) in the central nervous system (CNS). While these enzymes have been shown to be involved in physiological regulation of cerebral vascular tone, excessive ROS produced by Nox1-5 play a critical role in blood–brain barrier (BBB) dysfunction in numerous neuropathologies. Nox-derived ROS have been implicated in mediating matrix metalloprotease (MMP) activation, downregulation of junctional complexes between adjacent brain endothelial cells and brain endothelial cell apoptosis, leading to brain microvascular endothelial barrier dysfunction and consequently, increases in BBB permeability. In this review, we will highlight recent findings on the role played by these enzymes in BBB disruption induced by ischemic stroke.
Epitranscriptome Analysis of Oxidative Stressed Retinal Epithelial Cells Depicted a Possible RNA Editing Landscape of Retinal Degeneration
Authors: Donato Luigi , Scimone Concetta , Alibrandi Simona , Scalinci Sergio Zaccaria , Rinaldi Carmela , D’Angelo Rosalia , Sidoti Antonina
Published: October 2022

Oxidative stress represents one of the principal causes of inherited retinal dystrophies, with many related molecular mechanisms still unknown. We investigated the posttranscriptional RNA editing landscape of human retinal pigment epithelium cells (RPE) exposed to the oxidant agent N-retinylidene-N-retinyl ethanolamine (A2E) for 1 h, 2 h, 3 h and 6 h. Using a transcriptomic approach, refined with a specific multialgorithm pipeline, 62,880 already annotated and de novo RNA editing sites within about 3000 genes were identified among all samples. Approximately 19% of these RNA editing sites were found within 3′ UTR, including sites common to all time points that were predicted to change the binding capacity of 359 miRNAs towards 9654 target genes. A2E exposure also determined significant gene expression differences in deaminase family ADAR, APOBEC and ADAT members, involved in canonical and tRNA editing events. On GO and KEGG enrichment analyses, genes that showed different RNA editing levels are mainly involved in pathways strongly linked to a possible neovascularization of retinal tissue, with induced apoptosis mediated by the ECM and surface protein altered signaling. Collectively, this work demonstrated dynamic RNA editome profiles in RPE cells for the first time and shed more light on new mechanisms at the basis of retinal degeneration.
Two Distinct Superoxidase Dismutases (SOD) Secreted by the Helminth Parasite Fasciola hepatica Play Roles in Defence against Metabolic and Host Immune Cell-Derived Reactive Oxygen Species (ROS) during Growth and Development
Authors: Calvani Nichola Eliza Davies , De Marco Verissimo Carolina , Jewhurst Heather Louise , Cwiklinski Krystyna , Flaus Andrew , Dalton John Pius
Published: October 2022

The antioxidant superoxide dismutase (SOD) catalyses the dismutation of superoxide, a dangerous oxygen free radical, into hydrogen peroxide and molecular oxygen. Superoxide generation during the oxidative burst of the innate immune system is considered a key component of the host defence against invading pathogens. We demonstrate the presence and differential expression of two SODs in Fasciola hepatica, a leaderless cytosolic (FhSOD1) and an extracellular (FhSOD3) form containing a secretory signal peptide, suggesting that the parasites exploit these enzymes in distinct ways to counteract reactive oxygen species (ROS) produced by cellular metabolism and immune defences. Both enzymes are highly expressed by the infective newly excysted juvenile (NEJ) stages and are found in abundance in their excretory–secretory products (ES), but only FhSOD1 is present in adult ES, suggesting that the antioxidants have different functions and pathways of secretion, and are under separate temporal expression control during the migration, growth, and development of the parasite. Functionally, the recombinant FhSOD1 and FhSOD3 exhibit similar activity against superoxide to their mammalian counterparts. Confocal immuno-localisation studies demonstrated the presence of FhSOD1 and FhSOD3 on the NEJ tegument and parenchyma, supporting our suggestion that these enzymes are secreted during host invasion to protect the parasites from the harmful oxidative bursts produced by the activated innate immune response. By producing superoxide enzymatically in vitro, we were able to demonstrate robust killing of F. hepatica NEJ within 24 h post-excystment, and that the lethal effect of ROS was nullified with the addition of SOD and catalase (the antioxidant enzyme responsible for the dismutation of hydrogen peroxide, a by-product of the SOD reaction). This study further elucidates the mechanism by which F. hepatica protects against ROS derived from cellular metabolism and how the parasite could mitigate damage caused by the host’s immune response to benefit its survival.
The Use of the Coenzyme Q10 as a Food Supplement in the Management of Fibromyalgia: A Critical Review
Authors: Campisi Luca , La Motta Concettina
Published: October 2022

The coenzyme Q10 is a naturally occurring benzoquinone derivative widely prescribed as a food supplement for different physical conditions and pathologies. This review aims to sum up the key structural and functional characteristics of Q10, taking stock of its use in people affected by fibromyalgia. A thorough survey has been conducted, using Pubmed, Scifinder, and ClinicalTrials.gov as the reference research applications and registry database, respectively. Original articles, reviews, and editorials published within the last 15 years, as well as open clinical investigations in the field, if any, were analyzed to point out the lights and shadows of this kind of supplementation as they emerge from the literature.
Selection of Potential Probiotic Yeasts from Dry-Cured Xuanwei Ham and Identification of Yeast-Derived Antioxidant Peptides
Authors: Cai Jiaming , Xing Lujuan , Zhang Wangang , Fu Lijuan , Zhang Jian
Published: October 2022

The aim of this study was to select potential probiotic yeasts from dry-cured Xuanwei ham and investigate yeast-derived antioxidant peptides. The results showed that two strains (XHY69 and XHY79) were selected as potential probiotic yeasts and identified as Yamadazyma triangularis. The two yeasts showed tolerance under pH 2.5 and 1% bile salt, in addition to protease activity, auto-aggregation, antibacterial, and antioxidant activities. The peptide fraction (MW < 3 kDa) isolated from XHY69 fermentation broth, named XHY69AP, showed higher radical scavenging activities than glutathione at a concentration of 4.5 mg/mL (p < 0.05). The fraction (AP-D10) was purified from XHY69AP by gel filtration chromatography and reversed-phase high performance liquid chromatography, and then further identified by a UHPLC-LTQ-Orbitrap mass spectrometer. The molecular weight of all 55 purified sequences was distributed between 0.370 and 0.735 kDa. Among these seven novel peptides, Tyr-Pro-Leu-Pro (YPLP), Ala-Gly-Pro-Leu (AGPL), Gly-Pro-Phe-Pro (GPFP), and Ala-Pro-Gly-Gly-Phe (APGGF) were identified. All sequences were abundant in hydrophobic amino acids, especially proline residue. Among these novel peptides, YPLP possessed the highest ABTS scavenging rate (75.48%). The present work selects two new probiotic potential yeasts from dry-cured Xuanwei ham that are effective to yield novel antioxidant peptides.
Trends in Gliosis in Obesity, and the Role of Antioxidants as a Therapeutic Alternative
Authors: Bandala Cindy , Cárdenas-Rodríguez Noemi , Reyes-Long Samuel , Cortes-Altamirano José Luis , Garciadiego-Cázares David , Lara-Padilla Eleazar , Ibáñez-Cervantes Gabriela , Mancilla-Ramírez Javier , Gómez-Manzo Saul , Alfaro-Rodríguez Alfonso
Published: October 2022

Obesity remains a global health problem. Chronic low-grade inflammation in this pathology has been related to comorbidities such as cognitive alterations that, in the long term, can lead to neurodegenerative diseases. Neuroinflammation or gliosis in patients with obesity and type 2 diabetes mellitus has been related to the effect of adipokines, high lipid levels and glucose, which increase the production of free radicals. Cerebral gliosis can be a risk factor for developing neurodegenerative diseases, and antioxidants could be an alternative for the prevention and treatment of neural comorbidities in obese patients. Aim: Identify the immunological and oxidative stress mechanisms that produce gliosis in patients with obesity and propose antioxidants as an alternative to reducing neuroinflammation. Method: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index for research on the physiopathology of gliosis in obese patients and for the possible role of antioxidants in its management. Conclusion: Patients with obesity can develop neuroinflammation, conditioned by various adipokines, excess lipids and glucose, which results in an increase in free radicals that must be neutralized with antioxidants to reduce gliosis and the risk of long-term neurodegeneration.
Glutathione and Glutaredoxin in Redox Regulation and Cell Signaling of the Lens
Authors: Lou Marjorie F.
Published: October 2022

The ocular lens has a very high content of the antioxidant glutathione (GSH) and the enzymes that can recycle its oxidized form, glutathione disulfide (GSSG), for further use. It can be synthesized in the lens and, in part, transported from the neighboring anterior aqueous humor and posterior vitreous body. GSH is known to protect the thiols of the structural lens crystallin proteins from oxidation by reactive oxygen species (ROS) so the lens can maintain its transparency for proper visual function. Age-related lens opacity or senile cataract is the major visual impairment in the general population, and its cause is closely associated with aging and a constant exposure to environmental oxidative stress, such as ultraviolet light and the metabolic end product, H2O2. The mechanism for senile cataractogenesis has been hypothesized as the results of oxidation-induced protein-thiol mixed disulfide formation, such as protein-S-S-glutathione and protein-S-S-cysteine mixed disulfides, which if not reduced in time, can change the protein conformation to allow cascading modifications of various kinds leading to protein–protein aggregation and insolubilization. The consequence of such changes in lens structural proteins is lens opacity. Besides GSH, the lens has several antioxidation defense enzymes that can repair oxidation damage. One of the specific redox regulating enzymes that has been recently identified is thioltransferase (glutaredoxin 1), which works in concert with GSH, to reduce the oxidative stress as well as to regulate thiol/disulfide redox balance by preventing protein-thiol mixed disulfide accumulation in the lens. This oxidation-resistant and inducible enzyme has multiple physiological functions. In addition to protecting structural proteins and metabolic enzymes, it is able to regulate the redox signaling of the cells during growth factor-stimulated cell proliferation and other cellular functions. This review article focuses on describing the redox regulating functions of GSH and the thioltransferase enzyme in the ocular lens.
Analysis of the Antioxidant Composition of Low Molecular Weight Metabolites from the Agarolytic Bacterium Alteromonas macleodii QZ9-9: Possibilities for High-Added Value Utilization of Macroalgae
Authors: Wang Xinyi , Feng Ziqiao , Li Chenhui , Cai Xiaoni , Long Hao , Zhang Xiang , Huang Aiyou , Zeng Yanhua , Ren Wei , Xie Zhenyu
Published: October 2022

Agar accounts for ~60% of the dry weight of some red macroalgae, and the breakdown of this kind of polysaccharide releases high-value compounds; therefore, the resource utilization of agar is of great significance to improve the added value of these macroalgae. Herein, Alteromonas macleodii QZ9-9 isolated from tropical Gracilaria hainanensis in Hainan Island was characterized as an agarolytic bacterium, which displayed a high agar-degrading activity. The highest diameters of the degradation zones of the A. macleodii QZ9-9 and its extracellular-agarase (12.16 U/mL) were 41.46 mm and 22.89 mm, respectively, and the first-order degradation rate constants of those were 0.02 h−1 and 0.77 U−1, respectively. Importantly, the fermentation products of A. macleodii QZ9-9 exhibited antioxidant activity, and the peak of DPPH scavenging activity of 50 h fermentation products of this strain was up to 50.79% in the reaction for 1 h; the DPPH scavenging activity of low molecule metabolites (≤3 kDa) in particular was up to ~85.85%. A total of 766 metabolites were detected in the low molecule metabolites by metabolomics. The peptide-like metabolites, such as prolyl–histidine, isoleucyl–histidine, isoleucyl–proline and arginyl–proline, and the antioxidant maculosin were found in the top 20 metabolites with relatively high abundance. Additionally, the antioxidant activity of maculosin was further verified in this work. We concluded that the low molecule metabolites of A. macleodii QZ9-9 with relatively high antioxidant activity are interesting candidates for preparing desirable non-toxic antioxidants, thereby facilitating the high value-added utilization of macroalgae in the fields of cosmetic, food preservation, and pharmaceutical industries.
Mitochondria Biology in Reproductive Function
Authors: Tatone Carla , Di Emidio Giovanna
Published: October 2022

Mitochondria are multitasking organelles involved in the maintenance of cell homeostasis [...]
Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation
Authors: Heo Eun-Young , Lee Kyoung-Hee , Woo Jisu , Kim Jiyeon , Lee Chang-Hoon , Lee Kyung-Jin , Kim Yun-Kyu , Yoo Chul-Gyu
Published: October 2022

Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.
Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by MnSOD Ala-9Val Gene Polymorphism
Authors: Wang Dong Mei , Zhu Rong Rong , Tian Yang , Uludag Kadir , Chen Jia Jing , Zhou Hui Xia , Wang Li , Kosten Thomas R. , Zhang Xiang Yang
Published: October 2022

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and MnSOD Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients’ psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. MnSOD Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by MnSOD Ala-9Val polymorphism.
Antiproliferation Effects of Marine-Sponge-Derived Methanol Extract of Theonella swinhoei in Oral Cancer Cells In Vitro
Authors: Shiau Jun-Ping , Chuang Ya-Ting , Tang Jen-Yang , Chen Shu-Rong , Hou Ming-Feng , Jeng Jiiang-Huei , Cheng Yuan-Bin , Chang Hsueh-Wei
Published: October 2022

The purpose of this study aimed to assess the antiproliferation effects of methanol extract of T. swinhoei (METS) and explore the detailed responses of oral cancer cells compared to normal cells. METS effectively inhibits the cell proliferation of oral cancer cells but does not affect normal cell viability, exhibiting preferential antiproliferation function. METS exerted more subG1 accumulation, apoptosis induction, cellular and mitochondrial oxidative stress, and DNA damage than normal cells, reverted by oxidative stress inhibitor N-acetylcysteine. This METS-caused oxidative stress was validated to attribute to the downregulation of glutathione. METS activated both extrinsic and intrinsic caspases. DNA double-strand breaks (γH2AX) and oxidative DNA damage (8-hydroxy-2-deoxyguanosine) were stimulated by METS. Therefore, for the first time, this investigation shed light on exploring the functions and responses of preferential antiproliferation of METS in oral cancer cells.
Vitamin E Lipid-Based Nanodevices as a Tool for Ovine Sperm Protection against Oxidative Stress: Impact on Sperm Motility
Authors: Jurado-Campos Alejandro , Soria-Meneses Pedro Javier , Arenas-Moreira María , Alonso-Moreno Carlos , Bravo Iván , Rodríguez-Robledo Virginia , Sánchez-Ajofrín Irene , Soler Ana Josefa , Garde José Julián , Fernández-Santos María del Rocío
Published: October 2022

The advent of nanotechnology in the field of animal reproduction has led to the development of safer and more efficient therapies. The use of nanotechnology allows us to avoid the detrimental effects of certain traditional antioxidants, such as Vitamin E. Its hydrophobic nature makes mandatory the use of organic solvents, which are toxic to sperm cells. This study aims to evaluate the efficiency of vitamin E nanoemulsions (NE) on ram (Ovis aries) spermatozoa. For this purpose, the effect of three NE concentrations (6, 12, and 24 mM) were assessed on sperm of 10 mature rams of the Manchega breed. Sperm samples were collected by artificial vagina, pooled, and diluted in Bovine Gamete Medium. The samples were stored at 37 °C and assessed at 0, 4, 8, and 24 h under oxidative stress conditions (100 µM Fe2+/ascorbate). Motility (CASA), viability (YO-PRO/IP), acrosomal integrity (PNA-FITC/IP), mitochondrial membrane potential (Mitotracker Deep Red 633), lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®®) were assessed. A linear mixed-effects models were used to analyze the effects of time, NE, and oxidant (fixed factors) on sperm parameters, and a random effect on the male was also included in the model with Tukey’s post hoc test. Protection of ram spermatozoa with NE resulted in a more vigorous motility under oxidative stress conditions with respect Control and Free vitamin E, while preventing the deleterious effects of oxidative stress coming from the production of free radicals and lipid peroxidation. These results ascertain the high relevance of the use of delivery systems for sperm physiology preservation in the context of assisted reproduction techniques.
Analysis of Antioxidant Constituents from Ilex rotunda and Evaluation of Their Blood–Brain Barrier Permeability
Authors: Kim Chang-Kwon , Ahn Jeongjun , Yu Jayeon , Le DucDat , Han Sanghee , Lee Mina
Published: October 2022

Ilex rotunda Thunb., has been used to treat common cold, tonsillitis, and eczema. It is also a source of antioxidants. However, information regarding its antioxidative phytochemical composition is still incomplete and limited. In this present study, we initially determined DPPH radical scavenging activity of the extracts of I. rotunda fruits, twigs, and leaves. Among them, the twig extract exhibited a potential of antioxidant capacity. Based on antioxidant effect guided experiments, extraction condition using 80% EtOH was then optimized. DPPH and ABTS radical scavenging assays were also performed for fractions. The n-butanol fraction showed the highest antioxidant effect. Using chromatographic methods, eight marker compounds (1–8) were further isolated. Their structures were determined by spectroscopic and mass data. Method validation was employed to quantitate contents of these eight marker compounds. Subsequently, the HPLC-DPPH method was used to evaluate the contribution of certain compounds to total antioxidant activity of the extract. Lastly, parallel artificial membrane permeability assay for blood–brain barrier (PAMPA-BBB) was applied to investigate brain-penetrable antioxidants from I. rotunda extract. As a result, compound 7 (4,5-dicaffeoylquinic acid) showed significant antioxidant activity and penetration across the BBB via transcellular passive diffusion. Our findings suggested that compound 7 can be used as a therapeutic potential candidate in natural product-based central nervous system (CNS) drug discovery.
The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders
Authors: Trinchese Giovanna , Cimmino Fabiano , Cavaliere Gina , Catapano Angela , Fogliano Chiara , Lama Adriano , Pirozzi Claudio , Cristiano Claudia , Russo Roberto , Petrella Lidia , Meli Rosaria , Mattace Raso Giuseppina , Crispino Marianna , Avallone Bice , Mollica Maria Pina
Published: October 2022

The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut–brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain development, mood and cognitive functions. The liver, with its key role in inflammatory and metabolic states, represents the crucial metabolic organ in this crosstalk. Indeed, through the portal vein, the liver receives not only nutrients but also numerous factors derived from the gut and visceral adipose tissue, which modulate metabolism and hepatic mitochondrial functions. Here, we investigated, in an animal model of ASD (BTBR mice), the involvement of hepatic mitochondria in the regulation of inflammatory state and liver damage. We observed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, and marked mitochondrial fission in BTBR mice. Our preliminary study provides a better understanding of the pathophysiology of ASD and could open the way to identifying hepatic mitochondria as targets for innovative therapeutic strategies for the disease.
Single and Combined Associations of Plasma and Urine Essential Trace Elements (Zn, Cu, Se, and Mn) with Cardiovascular Risk Factors in a Mediterranean Population
Authors: Barragán Rocío , Sánchez-González Cristina , Aranda Pilar , Sorlí José V. , Asensio Eva M. , Portolés Olga , Ortega-Azorín Carolina , Villamil Laura V. , Coltell Oscar , Llopis Juan , Rivas-García Lorenzo , Corella Dolores
Published: October 2022

Trace elements are micronutrients that are required in very small quantities through diet but are crucial for the prevention of acute and chronic diseases. Despite the fact that initial studies demonstrated inverse associations between some of the most important essential trace elements (Zn, Cu, Se, and Mn) and cardiovascular disease, several recent studies have reported a direct association with cardiovascular risk factors due to the fact that these elements can act as both antioxidants and pro-oxidants, depending on several factors. This study aims to investigate the association between plasma and urine concentrations of trace elements and cardiovascular risk factors in a general population from the Mediterranean region, including 484 men and women aged 18–80 years and considering trace elements individually and as joint exposure. Zn, Cu, Se, and Mn were determined in plasma and urine using an inductively coupled plasma mass spectrometer (ICP-MS). Single and combined analysis of trace elements with plasma lipid, blood pressure, diabetes, and anthropometric variables was undertaken. Principal component analysis, quantile-based g-computation, and calculation of trace element risk scores (TERS) were used for the combined analyses. Models were adjusted for covariates. In single trace element models, we found statistically significant associations between plasma Se and increased total cholesterol and systolic blood pressure; plasma Cu and increased triglycerides and body mass index; and urine Zn and increased glucose. Moreover, in the joint exposure analysis using quantile g-computation and TERS, the combined plasma levels of Zn, Cu, Se (directly), and Mn (inversely) were strongly associated with hypercholesterolemia (OR: 2.03; 95%CI: 1.37–2.99; p < 0.001 per quartile increase in the g-computation approach). The analysis of urine mixtures revealed a significant relationship with both fasting glucose and diabetes (OR: 1.91; 95%CI: 1.01–3.04; p = 0.046). In conclusion, in this Mediterranean population, the combined effect of higher plasma trace element levels (primarily Se, Cu, and Zn) was directly associated with elevated plasma lipids, whereas the mixture effect in urine was primarily associated with plasma glucose. Both parameters are relevant cardiovascular risk factors, and increased trace element exposures should be considered with caution.
Alhagi maurorum Ethanolic Extract Rescues Hepato-Neurotoxicity and Neurobehavioral Alterations Induced by Lead in Rats via Abrogating Oxidative Stress and the Caspase-3-Dependent Apoptotic Pathway
Authors: Saber Taghred M. , Abo-Elmaaty Azza M. A. , Said Enas N. , Beheiry Rasha R. , Moselhy Attia A. A. , Abdelgawad Fathy Elsayed , Arisha Mariam H. , Saber Taisir , Arisha Ahmed Hamed , Fahmy Esraa M.
Published: October 2022

This work investigated the probable protective effect of an Alhagi maurorum ethanolic extract on the hepatotoxicity and neurotoxicity accompanied by neurobehavioral deficits caused by lead in rats. Rats in four groups were orally administered distilled water, ethanolic extract of A. maurorum (300 mg/kg BW daily), lead (100 mg/kg BW daily for 3 months), and lead + A. maurorum extract. The results demonstrated that lead exposure resulted in elevated locomotor activities and sensorimotor deficits associated with a decrease in brain dopamine levels. Moreover, lead exposure significantly increased liver function markers. In addition, the lead-treated rats exhibited extensive liver and brain histological changes and apoptosis. The lead treatment also triggered oxidative stress, as demonstrated by the increase in malondialdehyde (MDA) concentrations with a remarkable reduction in the activities of antioxidant enzymes, reduced glutathione (GSH) levels, and transcriptional mRNA levels of antioxidant genes in the liver and brain. Nevertheless, co-treatment with the A. maurorum extract significantly ameliorated the lead-induced toxic effects. These findings indicate that the A. maurorum extract has the ability to protect hepatic and brain tissues against lead exposure in rats through the attenuation of apoptosis and oxidative stress.
Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid
Authors: Gęgotek Agnieszka , Skrzydlewska Elżbieta
Published: October 2022

Ascorbic acid, as a one of the basic exogenous vitamins, occurs in the body in the form of ascorbate, known for its strong antioxidant and anti-inflammatory properties. The presented review shows not only the importance of ascorbate as a free radical scavenger but also summarizes its antioxidant action based on other mechanisms, including the activation of intracellular antioxidant systems and its effect on the NFκB/TNFα pathway and apoptosis. Ascorbate interacts with small-molecule antioxidants, including tocopherol, glutathione, and thioredoxin; it can also stimulate biosynthesis and the activation of antioxidant enzymes, such as superoxide dismutase, catalase, or glutathione peroxidase. Moreover, ascorbate promotes the activity of transcription factors (Nrf2, Ref-1, AP-1), which enables the expression of genes encoding antioxidant proteins. Additionally, it supports the action of other exogenous antioxidants, mainly polyphenols. In this regard, both DNA, proteins, and lipids are protected against oxidation, leading to an inflammatory reaction and even cell death. Although ascorbate has strong antioxidant properties, it can also have pro-oxidant effects in the presence of free transition metals. However, its role in the prevention of DNA mutation, inflammation, and cell apoptosis, especially in relation to cancer cells, is controversial.
Joint Embedding of Semantic and Statistical Features for Effective Code Search
Authors: Kong Xianglong , Kong Supeng , Yu Ming , Du Chengjie
Published: October 2022

Code search is an important approach to improve effectiveness and efficiency of software development. The current studies commonly search target code based on either semantic or statistical information in large datasets. Semantic and statistical information have hidden relationships between them since they describe code snippets from different perspectives. In this work, we propose a joint embedding model of semantic and statistical features to improve the effectiveness of code annotation. Then, we implement a code search engine, i.e., JessCS, based on the joint embedding model. We evaluate JessCS on more than 1 million lines of code snippets and corresponding descriptions. The experimental results show that JessCS performs more effective than UNIF-based approach, with at least 13% improvements on the studied metrics.
Deformation Detection and Attribution Analysis of Urban Areas near Dianchi Lake in Kunming Using the Time-Series InSAR Technique
Authors: Wang Junyu , Li Menghua , Yang Mengshi , Tang Bo-Hui
Published: October 2022

The main city of Kunming is located on the north bank of Dianchi Lake. The complex geological environment, large-scale construction, and expansion of the city in recent years have caused uneven land surface subsidence and threatened public safety. In this study, Sentinel-1 ascending and descending orbit datasets were collected for the period of February 2018 to May 2021. The characteristics of surface displacement in the Kunming downtown area were monitored using the time-series interferometric synthetic aperture radar (InSAR) technique, and attribution analysis was performed. It was found that areas with more severe surface settlement were concentrated in the International Exhibition Center area and the large, newly built communities near Dianchi Lake and the Xiaobanqiao Region. The multifactor attribution analysis results demonstrated that the subsidence areas are concentrated in urban villages and engineered, construction-intensive areas in the lakeside sedimentary layer area, with the maximum displacement rate reaching −23.12 mm/a in the line-of-sight direction of the Sentinel-1 ascending dataset. The reliability of the InSAR results was cross-validated with ascending and descending results. This study provides a scientific reference for urban development planning and potential geological disaster detection in Kunming.
Encapsulated Probiotics: Potential Techniques and Coating Materials for Non-Dairy Food Applications
Authors: Koh Wee Yin , Lim Xiao Xian , Tan Thuan-Chew , Kobun Rovina , Rasti Babak
Published: October 2022

The growing health awareness among consumers has increased the demand for non-dairy-based products containing probiotics. However, the incorporation of probiotics in non-dairy matrices is challenging, and probiotics tend to have a low survival rate in these matrices and subsequently perform poorly in the gastrointestinal system. Encapsulation of probiotics with a physical barrier could preserve the survivability of probiotics and subsequently improve delivery efficiency to the host. This article aimed to review the effectiveness of encapsulation techniques (coacervation, extrusion, emulsion, spray-drying, freeze-drying, fluidized bed coating, spray chilling, layer-by-layer, and co-encapsulation) and biomaterials (carbohydrate-, fat-, and protein-based) on the viability of probiotics under the harsh conditions of food processing, storage, and along the gastrointestinal passage. Recent studies on probiotic encapsulations using non-dairy food matrices, such as fruits, fruit and vegetable juices, fermented rice beverages, tea, jelly-like desserts, bakery products, sauces, and gum products, were also included in this review. Overall, co-encapsulation of probiotics with prebiotics was found to be effective in preserving the viability of probiotics in non-dairy food matrices. Encapsulation techniques could add value and widen the application of probiotics in the non-dairy food market and future perspectives in this area.
Conditional Generative Adversarial Networks with Total Variation and Color Correction for Generating Indonesian Face Photo from Sketch
Authors: Rizkinia Mia , Faustine Nathaniel , Okuda Masahiro
Published: October 2022

Historically, hand-drawn face sketches have been commonly used by Indonesia’s police force, especially to quickly describe a person’s facial features in searching for fugitives based on eyewitness testimony. Several studies have been performed, aiming to increase the effectiveness of the method, such as comparing the facial sketch with the all-points bulletin (DPO in Indonesian terminology) or generating a facial composite. However, making facial composites using an application takes quite a long time. Moreover, when these composites are directly compared to the DPO, the accuracy is insufficient, and thus, the technique requires further development. This study applies a conditional generative adversarial network (cGAN) to convert a face sketch image into a color face photo with an additional Total Variation (TV) term in the loss function to improve the visual quality of the resulting image. Furthermore, we apply a color correction to adjust the resulting skin tone similar to that of the ground truth. The face image dataset was collected from various sources matching Indonesian skin tone and facial features. We aim to provide a method for Indonesian face sketch-to-photo generation to visualize the facial features more accurately than the conventional method. This approach produces visually realistic photos from face sketches, as well as true skin tones.