bluuebunny/crossref_metadata_2025 huggingface dataset:
IPA-3: An Inhibitor of Diadenylate Cyclase of Streptococcus suis with Potent Antimicrobial Activity
Authors: Li Haotian , Li Tingting , Zou Wenjin , Ni Minghui , Hu Qiao , Qiu Xiuxiu , Yao Zhiming , Fan Jingyan , Li Lu , Huang Qi , Zhou Rui
Published: March 2022

Antimicrobial resistance (AMR) poses a huge threat to public health. The development of novel antibiotics is an effective strategy to tackle AMR. Cyclic diadenylate monophosphate (c-di-AMP) has recently been identified as an essential signal molecule for some important bacterial pathogens involved in various bacterial physiological processes, leading to its synthase diadenylate cyclase becoming an attractive antimicrobial drug target. In this study, based on the enzymatic activity of diadenylate cyclase of Streptococcus suis (ssDacA), we established a high-throughput method of screening for ssDacA inhibitors. Primary screening with a compound library containing 1133 compounds identified IPA-3 (2,2′-dihydroxy-1,1′-dinapthyldisulfide) as an ssDacA inhibitor. High-performance liquid chromatography (HPLC) analysis further indicated that IPA-3 could inhibit the production of c-di-AMP by ssDacA in vitro in a dose-dependent manner. Notably, it was demonstrated that IPA-3 could significantly inhibit the growth of several Gram-positive bacteria which harbor an essential diadenylate cyclase but not E. coli, which is devoid of the enzyme, or Streptococcus mutans, in which the diadenylate cyclase is not essential. Additionally, the binding site in ssDacA for IPA-3 was predicted by molecular docking, and contains residues that are relatively conserved in diadenylate cyclase of Gram-positive bacteria. Collectively, our results illustrate the feasibility of ssDacA as an antimicrobial target and consider IPA-3 as a promising starting point for the development of a novel antibacterial.
Microbial Spectra and Clinical Outcomes from Endoscopically Drained Pancreatic Fluid Collections: A Descriptive Cohort Study
Authors: Hentschel Viktoria , Walter Benjamin , Harder Noemi , Arnold Frank , Seufferlein Thomas , Wagner Martin , Müller Martin , Kleger Alexander
Published: March 2022

Pancreatic pseudocyst (PC) and walled-off necrosis (WON) are dreaded complications of acute pancreatitis. Standard therapy consists of endoscopic ultrasound-guided transmural placement of stents to expedite resolution through internal drainage of fluids or necrotic material. Either double pigtail plastic stents (DPPS) or lumen-apposing metal stents (LAMS), or a combination of both, are available for this purpose. The objective of this study was to examine the impact of different stent types on infection rates in addition to clinical outcome measures such as periprocedural adverse events. We conducted a retrospective study comprising 77 patients who had undergone endoscopic drainage for PC or WON in a pancreatitis tertiary referral center. Analysis revealed that both bacterial and fungal infections occurred more frequently in patients treated with LAMS with or without DPPS compared to DPPS only. The use of antibiotics and antimycotics followed the same pattern. Furthermore, a prolonged length of hospital stay and a higher likelihood of transfer to an intermediate care unit were observed in patients with LAMS with or without DPPS. These differences were eliminated if only WON patients were analyzed. Our data imply that the clinical course is primarily influenced by the complexity of the pancreatic fluid collection (PFC) itself rather than the stent type. Prospective large-scale cohort studies are mandatory to underpin these findings.
Assessment of Melatonin-Cultured Collagen/Chitosan Scaffolds Cross-Linked by a Glyoxal Solution as Biomaterials for Wound Healing
Authors: Kaczmarek-Szczepańska Beata , Pin Judith M. , Zasada Lidia , Sonne Mauritz M. , Reiter Russel J. , Slominski Andrzej T. , Steinbrink Kerstin , Kleszczyński Konrad
Published: March 2022

Chitosan (CTS) and collagen (Coll) are natural biomaterials that have been extensively used in tissue engineering or wound healing applications, either separately or as composite materials. Most methods to fabricate CTS/Coll matrices employ chemical crosslinking to obtain solid and stable scaffolds with the necessary porosity and mechanical properties to facilitate regeneration. In this study, we comparatively assessed the physicochemical properties of 3D scaffolds loaded with a cross-linker, glyoxal. Using a scanning electron microscope, we evaluated the microstructure of resultant matrices and their mechanistic testing by the determination of the compressive modulus (Emod), the maximum force (Fmax), thermogravimetric analysis (TG), Fourier Transform Infrared Spectroscopy–Attenuated Total Reflectance (FTIR-ATR), and proliferation rate in vitro using human epidermal keratinocytes and dermal fibroblasts cultured in presence of melatonin solution (10−5 M). We observed that enhanced content of collagen (50CTS/50Coll or 20CTS/80Coll compared to 80CTS/20Coll) significantly elevated the physicochemical capacities of resultant materials. Besides, presence of 5% glyoxal increased porosity, Emod and Fmax, compared to scaffolds without glyoxal. Finally, keratinocytes and dermal fibroblasts cultured on subjected matrices in presence of melatonin revealed a prominently enhanced growth rate. This indicates that the combination of glyoxal and melatonin make it imperative to consider these materials as a promising approach for targeting skin tissue engineering or regenerative dermatology.
The Antioxidant Selenoprotein T Mimetic, PSELT, Induces Preconditioning-like Myocardial Protection by Relieving Endoplasmic-Reticulum Stress
Authors: Rocca Carmine , De Bartolo Anna , Granieri Maria Concetta , Rago Vittoria , Amelio Daniela , Falbo Flavia , Malivindi Rocco , Mazza Rosa , Cerra Maria Carmela , Boukhzar Loubna , Lefranc Benjamin , Leprince Jérôme , Anouar Youssef , Angelone Tommaso
Published: March 2022

Oxidative stress and endoplasmic reticulum stress (ERS) are strictly involved in myocardial ischemia/reperfusion (MI/R). Selenoprotein T (SELENOT), a vital thioredoxin-like selenoprotein, is crucial for ER homeostasis and cardiomyocyte differentiation and protection, likely acting as a redox-sensing protein during MI/R. Here, we designed a small peptide (PSELT), encompassing the redox site of SELENOT, and investigated whether its pre-conditioning cardioprotective effect resulted from modulating ERS during I/R. The Langendorff rat heart model was employed for hemodynamic analysis, while mechanistic studies were performed in perfused hearts and H9c2 cardiomyoblasts. PSELT improved the post-ischemic contractile recovery, reducing infarct size and LDH release with and without the ERS inducer tunicamycin (TM). Mechanistically, I/R and TM upregulated SELENOT expression, which was further enhanced by PSELT. PSELT also prevented the expression of the ERS markers CHOP and ATF6, reduced cardiac lipid peroxidation and protein oxidation, and increased SOD and catalase activities. An inert PSELT (I-PSELT) lacking selenocysteine was ineffective. In H9c2 cells, H2O2 decreased cell viability and SELENOT expression, while PSELT rescued protein levels protecting against cell death. In SELENOT-deficient H9c2 cells, H2O2 exacerbated cell death, that was partially mitigated by PSELT. Microscopy analysis revealed that a fluorescent form of PSELT was internalized into cardiomyocytes with a perinuclear distribution. Conclusions: The cell-permeable PSELT is able to induce pharmacological preconditioning cardioprotection by mitigating ERS and oxidative stress, and by regulating endogenous SELENOT.
Positive Aspects of Oxidative Stress at Different Levels of the Human Body: A Review
Authors: Jîtcă George , Ősz Bianca E. , Tero-Vescan Amelia , Miklos Amalia Pușcaș , Rusz Carmen-Maria , Bătrînu Mădălina-Georgiana , Vari Camil E.
Published: March 2022

Oxidative stress is the subject of numerous studies, most of them focusing on the negative effects exerted at both molecular and cellular levels, ignoring the possible benefits of free radicals. More and more people admit to having heard of the term “oxidative stress”, but few of them understand the meaning of it. We summarized and analyzed the published literature data in order to emphasize the importance and adaptation mechanisms of basal oxidative stress. This review aims to provide an overview of the mechanisms underlying the positive effects of oxidative stress, highlighting these effects, as well as the risks for the population consuming higher doses than the recommended daily intake of antioxidants. The biological dose–response curve in oxidative stress is unpredictable as reactive species are clearly responsible for cellular degradation, whereas antioxidant therapies can alleviate senescence by maintaining redox balance; nevertheless, excessive doses of the latter can modify the redox balance of the cell, leading to a negative outcome. It can be stated that the presence of oxidative status or oxidative stress is a physiological condition with well-defined roles, yet these have been insufficiently researched and explored. The involvement of reactive oxygen species in the pathophysiology of some associated diseases is well-known and the involvement of antioxidant therapies in the processes of senescence, apoptosis, autophagy, and the maintenance of cellular homeostasis cannot be denied. All data in this review support the idea that oxidative stress is an undesirable phenomenon in high and long-term concentrations, but regular exposure is consistent with the hormetic theory.
Evaluation of Label-Free Confocal Raman Microspectroscopy for Monitoring Oxidative Stress In Vitro in Live Human Cancer Cells
Authors: Surmacki Jakub Maciej , Quiros-Gonzalez Isabel , Bohndiek Sarah Elizabeth
Published: March 2022

Understanding the impact of free radicals and antioxidants in cell biology is vital; however, noninvasive nonperturbative imaging of oxidative stress remains a challenge. Here, we evaluated the ability of label-free Raman spectroscopy to monitor redox biochemical changes in antioxidant (N-acetyl-l-cysteine, NAC) and pro-oxidant (tert-butyl hydroperoxide, TBHP) environments. Cellular changes were compared to fluorescence microscopy using CellROX Orange as a marker of oxidative stress. We also investigated the influence of cell media with and without serum. Incubation of cells with NAC increased the Raman signal at 498 cm−1 from S-S disulphide stretching mode, one of the most important redox-related sensors. Exposure of cells to TBHP resulted in decreased Raman spectral signals from DNA/proteins and lipids (at 784, 1094, 1003, 1606, 1658 and 718, 1264, 1301, 1440, 1746 cm−1). Using partial least squares–discriminant analysis, we showed that Raman spectroscopy can achieve sensitivity up to 96.7%, 94.8% and 91.6% for control, NAC and TBHP conditions, respectively, with specificity of up to 93.5, 90.1% and 87.9%. Our results indicate that Raman spectroscopy can directly measure the effect of NAC antioxidants and accurately characterize the intracellular conditions associated with TBHP-induced oxidative stress, including lipid peroxidation and DNA damage.
Effects of High Starch and Supplementation of an Olive Extract on the Growth Performance, Hepatic Antioxidant Capacity and Lipid Metabolism of Largemouth Bass (Micropterus salmoides)
Authors: Liang Xiaofang , Chen Pei , Wu Xiaoliang , Xing Shujuan , Morais Sofia , He Maolong , Gu Xu , Xue Min
Published: March 2022

An 8-week feeding trial was conducted to investigate the effects of high-starch diets and the supplementation of an olive extract (OE) on the growth performance, liver health and lipid metabolism of largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were prepared: two basal diets containing low (9.0%) and high (14.4%) levels of starch (named as LS and HS), and 0.125% OE was supplemented to each basal diet (named LSOE and HSOE). The results show that high-starch diets had significant negative effects on growth performance, with lower FR, SGR and higher FCR, whereas OE significantly lowered FCR, determined by two-way ANOVA analysis. High-starch diets induced oxidative stress, inflammatory response and liver function injury, with significant increases in the content of plasmatic AKP, AST, ALT, hepatic SOD and MDA, and up-regulation of hepatic TNFα, IL1β, and TGFβ1 gene expression. In addition, a high-starch diet decreased the phosphorylation of AMPK and upregulated the expression of SREBP, together with higher hepatic liver lipid and HSI. The oxidative stress and lipid metabolism disorders indicate metabolic liver disease (MLD) of largemouth bass fed high-starch diets. Feeding on OE-supplemented diets increased the hepatic antioxidant capacity by decreasing the content of MDA and SOD. Fish fed the HSOE diet had an activated phosphorylation of JNK and decreased expression of pro-inflammatory IL1β compared with those fed the HS diet, which strongly indicated that the degree of inflammatory responses was reduced after OE supplementation. Interestingly, this study demonstrated that OE regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (ACC1 and FASN) and promoting lipolysis (ATGL) and β-oxidation (CPT1α) to prevent TG accumulation. In conclusion, high-starch feed induced oxidative stress and lipid metabolic disorder of largemouth bass, while supplementation with OE improved its antioxidant capacity, anti-inflammatory responses and lipid metabolism. However, hepatic histopathological results suggested that OE supplementation could not completely repair the MLD caused by the high level of starch in largemouth bass.
Bioactive Phytochemicals and Quenching Activity of Radicals in Selected Drought-Resistant Amaranthus tricolor Vegetable Amaranth
Authors: Sarker Umakanta , Oba Shinya , Ercisli Sezai , Assouguem Amine , Alotaibi Amal , Ullah Riaz
Published: March 2022

Leafy vegetables are susceptible to drought stress. Amaranthus tricolor vegetables are resistant to abiotic stress, including drought, and are a source of ample natural phytochemicals of interest to the food industry due to their benefits to consumers’ health. Hence, the selected drought-resistant amaranth genotypes were evaluated for phytochemicals and antioxidant activity in an RCBD study with three replicates. The selected drought-resistant amaranth accessions contained ample carbohydrates, protein, moisture, and dietary fiber. We noticed many macroelements and microelements including iron, copper, manganese, zinc, sodium, molybdenum, boron, potassium, calcium, magnesium, phosphorus, and sulfur; adequate phytopigments, including betacyanins, betalains, betaxanthins, carotenoids, and chlorophylls; plentiful bioactive phytochemicals, including ascorbic acid, flavonoids, polyphenols, and beta-carotene; and antioxidant potential in the selected drought-resistant amaranth accessions. The drought-resistant amaranth accessions VA14 and VA16 were proven to have high ascorbic acid, beta-carotene, and polyphenol levels. The drought-resistant accessions VA12 and VA14 had high flavonoid levels. The drought-resistant accessions VA3, VA14, and VA16 had high AC both in regard to both DPPH and ABTS+. These drought-resistant accessions, VA3, VA14, and VA16, can be utilized as high-yielding varieties with antioxidant profiles for purposes of drinks. The correlation study revealed that bioactive phytopigments and phytochemicals of amaranth accessions had good free radical quenching capacity against 2,2′-azino-bis (3-ethylbenzothiazo-6-sulfonic acid) and diphenyl-1-picrylhydrazyl, equivalent to Trolox. It was revealed in the present study that these drought-resistant accessions contain plentiful proximate, nutraceuticals, phytopigments, bioactive phytochemicals, and antioxidant potentiality. Their drought resistance and quenching of ROS offer huge prospects for the promotion of health benefits and the feeding of communities in drought-prone semiarid and arid areas of the globe, especially those deficient in nutraceuticals, phytopigments, and antioxidants.
Combined Treatment with Bojungikgi-Tang and Riluzole Regulates Muscle Metabolism and Dysfunction in the hSOD1G93A Mouse Model
Authors: Cai Mudan , Yang Eun Jin
Published: March 2022

The progressive neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is characterized by muscle weakness and atrophy owing to selective motoneuron degeneration. The anti-glutamatergic drug, riluzole (RZ), is the standard-of-care treatment for ALS. Bojungikgi-tang (BJIGT), a traditional herbal formula, improves motor function and prolongs the survival of mice with ALS. As ALS is a multicomplex disease, effective therapies must target multiple mechanisms. Here, we evaluated the efficacy of a BJIGT/RZ combination (5-week treatment) in 2-month-old hSOD1G93A mice with ALS. We performed quantitative polymerase chain reaction, Western blotting, immunohistochemistry, and enzyme activity assays. BJIGT/RZ significantly attenuated inflammation, autophagy, and metabolic and mitochondrial dysfunctions in the gastrocnemius (GC) compared with the control. It reduced the mRNA and protein levels of muscle denervation-related proteins and creatine kinase levels. The total creatine level was significantly higher in the BJIGT/RZ-treated GC. Moreover, after BJIGT/RZ treatment, the number of Nissl-stained motoneurons and choline acetyl transferase-positive neurons in the spinal cord significantly increased via the regulation of proinflammatory cytokines. Collectively, the BJIGT/RZ treatment was superior to single-drug treatments in alleviating multiple ALS-related pathological mechanisms in the ALS mouse model. Overall, BJIGT can serve as a dietary supplement and be combined with RZ to achieve superior therapeutic effects against ALS.
A Review on Electrochemical Sensors and Biosensors Used in Assessing Antioxidant Activity
Authors: Munteanu Irina Georgiana , Apetrei Constantin
Published: March 2022

Currently, there is growing interest in screening and quantifying antioxidants from biological samples in the quest for natural and effective antioxidants to combat free radical-related pathological complications. Antioxidants play an important role in human health and provide a defense against many diseases. Due to the valuable dietary role of these compounds, the analysis and determination of their amount in food is of particular importance. In recent years, many attempts have been made to provide simple, fast, and economical analytical approaches for the on-site detection and determination of antioxidant activity in food antioxidants. In this regard, electrochemical sensors and biosensors are considered promising tools for antioxidant research due to their high sensitivity, fast response time, and ease of miniaturization; thus, they are used in a variety of fields, including food analysis, drug screening, and toxicity research. Herein, we review the recent advances in sensors and biosensors for the detection of antioxidants, underlying principles, and emphasizing advantages, along with limitations regarding the ability to discriminate between the specific antioxidant or quantifying total antioxidant content. In this work, both direct and indirect methods for antioxidants detecting with electrochemical sensors and biosensors are analyzed in detail. This review aims to prove how electrochemical sensors and biosensors represent reliable alternatives to conventional methods for antioxidant analysis.
Computational Models on Pathological Redox Signalling Driven by Pregnancy: A Review
Authors: Manna Samprikta , Ruano Camino S. M. , Hegenbarth Jana-Charlotte , Vaiman Daniel , Gupta Shailendra , McCarthy Fergus P. , Méhats Céline , McCarthy Cathal , Apicella Clara , Scheel Julia
Published: March 2022

Oxidative stress is associated with a myriad of diseases including pregnancy pathologies with long-term cardiovascular repercussions for both the mother and baby. Aberrant redox signalling coupled with deficient antioxidant defence leads to chronic molecular impairment. Abnormal placentation has been considered the primary source for reactive species; however, placental dysfunction has been deemed secondary to maternal cardiovascular maladaptation in pregnancy. While various therapeutic interventions, aimed at combating deregulated oxidative stress during pregnancy have shown promise in experimental models, they often result as inconclusive or detrimental in clinical trials, warranting the need for further research to identify candidates. The strengths and limitations of current experimental methods in redox research are discussed. Assessment of redox status and oxidative stress in experimental models and in clinical practice remains challenging; the state-of-the-art of computational models in this field is presented in this review, comparing static and dynamic models which provide functional information such as protein-protein interactions, as well as the impact of changes in molecular species on the redox-status of the system, respectively. Enhanced knowledge of redox biology in during pregnancy through computational modelling such as generation of Systems Biology Markup Language model which integrates existing models to a larger network in the context of placenta physiology.
15-F2t-Isoprostane Favors an Anti-Inflammatory Phenotype in RAW 264.7 Macrophages during Endotoxin Challenge
Authors: Putman Ashley K. , Contreras G. Andres
Published: March 2022

Dysregulated inflammation and oxidative stress are major underlying components of several diseases. Macrophages are critical effector cells in immune responses, functioning to progress and resolve inflammation during such diseases. These mononuclear cells regulate inflammatory responses by exhibiting a range of phenotypes that evolve with the process, first promoting inflammation but then switching to a proresolving subtype to restore tissue homeostasis. Furthermore, macrophages are a primary source of isoprostanes (IsoPs), a nonenzymatic byproduct of lipid peroxidation during inflammation. As highly sensitive and specific indicators of lipid damage, IsoPs are the gold standard biomarker of oxidative stress. However, the physiological role of IsoPs during inflammation is currently not well-established. This study determined how IsoPs affect macrophage phenotype during lipopolysaccharide (LPS) challenge. RAW 264.7 macrophages (n = 7) were challenged with 5 ng/mL LPS for 8 h, followed with or without 500 nM 15-F2t-IsoP for 1 h. Macrophage phenotype was determined using metabolic, transcriptomic, and proteomic markers. Phenotypic markers assessed included ATP production; transcription of proinflammatory Nos2, Il1β, and anti-inflammatory Il10; and translation markers IL1α and IL6 (proinflammatory) with G-CSF and IL17 (anti-inflammatory). Statistical analyses included one-way ANOVA followed by Tukey’s posthoc test. Significance was set at p < 0.05. In combination with LPS, 15-F2t-IsoP increased ATP production relative to LPS-only treated cells. Additionally, gene expression of Nos2 and Il1β were decreased while Il10 was increased. Cytokine production of IL6 was decreased while IL10, G-CSF, and IL17 were increased. Collectively, these results provide evidence that 15-F2t-IsoP promotes an anti-inflammatory macrophage phenotype during LPS challenge. These data support a novel physiological role of IsoPs, where these lipid mediators may participate in healing pathways during late-stage inflammation when they are elevated. Additionally, the promotion of an anti-inflammatory macrophage phenotype may contribute to preventing or mitigating inflammation during disease. Future studies should be directed towards defining the mechanisms in which IsoPs influence macrophage phenotype, such as receptor interactions and downstream signaling pathways.
Tandem Mass Tagging-Based Quantitative Proteomics Analysis Reveals Damage to the Liver and Brain of Hypophthalmichthys molitrix Exposed to Acute Hypoxia and Reoxygenation
Authors: Li Xiaohui , Feng Cui , Sha Hang , Zhou Tong , Zou Guiwei , Liang Hongwei
Published: March 2022

Aquaculture environments frequently experience hypoxia and subsequent reoxygenation conditions, which have significant effects on hypoxia-sensitive fish populations. In this study, hepatic biochemical activity indices in serum and the content of major neurotransmitters in the brain were altered markedly after acute hypoxia and reoxygenation exposure in silver carp (Hypophthalmichthys molitrix). Proteomics analysis of the liver showed that a number of immune-related and cytoskeletal organization-related proteins were downregulated, the ferroptosis pathway was activated, and several antioxidant molecules and detoxifying enzymes were upregulated. Proteomics analysis of the brain showed that somatostatin-1A (SST1A) was upregulated, dopamine-degrading enzyme catechol O methyltransferase (COMT) and ferritin, heavy subunit (FerH) were downregulated, and the levels of proteins involved in the nervous system were changed in different ways. In conclusion, these findings highlight that hypoxia–reoxygenation has potential adverse effects on growth, locomotion, immunity, and reproduction of silver carp, and represents a serious threat to liver and brain function, possibly via ferroptosis, oxidative stress, and cytoskeleton destruction in the liver, and abnormal expression of susceptibility genes for neurodegenerative disorders in the brain. Our present findings provide clues to the mechanisms of hypoxia and reoxygenation damage in the brain and liver of hypoxia-sensitive fish. They could also be used to develop methods to reduce hypoxia or reoxygenation injury to fish.
A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease
Authors: Mohammed Chrysan J. , Lamichhane Sabitri , Connolly Jacob A. , Soehnlen Sophia M. , Khalaf Fatimah K. , Malhotra Deepak , Haller Steven T. , Isailovic Dragan , Kennedy David J.
Published: March 2022

Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in the biomedical field. PON substrates are classified as organophosphates, aryl esters, and lactones based on their structure. While the established native physiological activity of PONs is its lactonase activity, the enzymes’ exact physiological substrates continue to be elucidated. All three PONs have antioxidant potential and play an important anti-atherosclerotic role in several diseases including cardiovascular diseases. PON3 is the last member of the family to be discovered and is also the least studied of the three genes. Unlike the other isoforms that have been reviewed extensively, there is a paucity of knowledge regarding PON3. Thus, the current review focuses on PON3 and summarizes the PON substrates, specific activities, kinetic parameters, and their association with cardiovascular as well as other diseases such as HIV and cancer.
Combinatorial Effects of the Natural Products Arctigenin, Chlorogenic Acid, and Cinnamaldehyde Commit Oxidation Assassination on Breast Cancer Cells
Authors: Schuster Caroline , Wolpert Nicholas , Moustaid-Moussa Naima , Gollahon Lauren S.
Published: March 2022

Major obstacles in current breast cancer treatment efficacy include the ability of breast cancer cells to develop resistance to chemotherapeutic drugs and the off-target cytotoxicity of these drugs on normal cells, leading to debilitating side effects. One major difference between cancer and normal cells is their metabolism, as cancer cells acquire glycolytic and mitochondrial metabolism alterations throughout tumorigenesis. In this study, we sought to exploit this metabolic difference by investigating alternative breast cancer treatment options based on the application of phytochemicals. Herein, we investigated three phytochemicals, namely cinnamaldehyde (CA), chlorogenic acid (CGA), and arctigenin (Arc), regarding their anti-breast-cancer properties. These phytochemicals were administered alone or in combination to MCF-7, MDA-MB-231, and HCC1419 breast cancer or normal MCF-10A and MCF-12F breast cells. Overall, our results indicated that the combination treatments showed stronger inhibitory effects on breast cancer cells versus single treatments. However, only treatments with CA (35 μM), CGA (250 μg/mL), and the combination of CA + CGA (35 μM + 250 μg/mL) showed no significant cytotoxic effects on normal mammary epithelial cells, suggesting that Arc was the driver of normal cell cytotoxicity in all other treatments. CA + CGA and, to a lesser extent, CGA alone effectively induced breast cancer cell death accompanied by decreases in mitochondrial membrane potential, increased mitochondrial superoxide, reduced mitochondrial and glycolytic ATP production, and led to significant changes in cellular and mitochondrial morphology. Altogether, the combination of CA + CGA was determined as the best anti-breast-cancer treatment strategy due to its strong anti-breast-cancer effects without strong adverse effects on normal mammary epithelial cells. This study provides evidence that targeting the mitochondria may be an effective anticancer treatment, and that using phytochemicals or combinations thereof offers new approaches in treating breast cancer that significantly reduce off-target effects on normal cells.
Effects of Phenolic Phytogenic Feed Additives on Certain Oxidative Damage Biomarkers and the Performance of Primiparous Sows Exposed to Heat Stress under Field Conditions
Authors: Papatsiros Vasileios G. , Katsogiannou Eleni G. , Papakonstantinou Georgios I. , Michel Alfred , Petrotos Konstantinos , Athanasiou Labrini V.
Published: March 2022

The aim of this study was to investigate the effects of two commercial phenolic phytogenic feed additives (PFAs) on sows under heat stress conditions of high summer temperatures for seven days before and seven days after the farrowing. The PFA-1 product was a mixture based on the plants Emblica officinalis, Foeniculum vulgare, Citrus sinensis and nut fiber, while the PFA-2 product was a mixture based on plants Andrographis paniculata, Glycyrrhizia glabra, Tinospora cordifolia and nut fiber. A total of 48 primiparous sows were divided into three groups: T1-control group: regular gestation (GF) and lactation feed (LF); T2 group: regular GF and LF supplemented with PFA-1; T3 group: regular GF and LF supplemented with PFA-2. Each sow in the T2 and T3 groups received 5 g daily of the PFA-1 and PFA-2 product, respectively, for seven days before and seven days after the farrowing. Blood samples were collected from all groups 24 h after farrowing. Thiobarbituric acid-–reactive substances (TBARS) and protein carbonyl (CARB) concentrations were determined in the sow plasma. The body condition scoring (BCS) and the backfat of sows on the farrowing and weaning days along with reproductive parameters and litter characteristics were recorded. The highest number of stillborn piglets and the largest interval from weaning to estrus were observed in the T1 group. The lowest number of alive 24 h after birth and weaning piglets and the lowest BCS and backfat at weaning were also recorded in the T1 group. TBARS and CARB concentrations were significant higher in the T1 group compared to all other groups. In conclusion, the use of phenolic PFAs seems to reduce oxidative damage caused by heat stress and ameliorate performance in primiparous sows.
UHPLC–MS Characterization, and Antioxidant and Nutritional Analysis of Cocoa Waste Flours from the Peruvian Amazon
Authors: Vargas-Arana Gabriel , Merino-Zegarra Claudia , Tang Miguel , Pertino Mariano Walter , Simirgiotis Mario J.
Published: March 2022

Cocoa (Theobroma cacao) is a food product used worldwide and a key raw material for chocolate manufacturing. Cocoa possesses bioactive compounds such as methylxanthines, flavonoids, procyanidins, and related molecules with medicinal or health-promoting properties. Cocoa shell and pod husk have been proposed as a by-product with several interesting bioactivities, and the gummy residue or glue (a sticky, gluey by-product known as “mucilage” in Spanish) is used to produce liquors and is eaten as a food in Perú. However, little is known about the chemical composition and bioactivity of flours made from Peruvian cocoa ecotype wastes such as those from the vein and pod husk of the fruits. This study aimed to characterize the in vitro antioxidant properties and nutritional values of flours made from the waste from a special ecotype of cocoa (CCN-51). The chemical fingerprinting was performed using UHPLC–HESI orbitrap mass spectrometry and allowed the detection of 51 compounds. GC-FID was used for the determination of individual fatty acid contents, and the antioxidant activity was assessed by several assays (DPPH, FRAP, and ABTS). The flours obtained were composed of a good amount of dietary fiber, carbohydrates, and minerals, as well as several bioactive polyphenolic compounds, fatty acids, and amino acids with nutraceutical properties, making the flours a rich and promising food as well as a good source for the preparation of functional foods or nutraceuticals.
The Different Contributors to Antioxidant Activity in Thermally Dried Flesh and Peel of Astringent Persimmon Fruit
Authors: Lim You Jin , Eom Seok Hyun
Published: March 2022

In the thermal-drying processing of astringent persimmon fruit, the tissue-specific changes in the key antioxidants have hardly been investigated, while they have been well investigated in the flesh. We report here the different patterns of the antioxidant activities in the thermally processed flesh and peel of astringent persimmon, with analyses of the carotenoids, the condensed and hydrolysable tannins, and the total phenolics and flavonoids. The persimmon powders presented different colors on the basis of the drying temperatures: brown in 30 °C; light yellow in 60 °C; and dark brown in 90 °C, respectively. Non-maillard reaction and reduction of carotenoids caused the light-yellow color of 60 °C dried persimmon. Thermal drying reduced the antioxidant activities of the flesh in a temperature-dependent manner, with decreases in the carotenoids, the condensed and hydrolysable tannins, and the total phenolics and flavonoids, whereas it enhanced the antioxidant activities of the peel. The increase in the antioxidant activities in the peel were mainly the result of the increase in the total phenolics by the thermal effect, and especially in the content of the hydrolysable tannins, although the thermal processing decreased the other components. The heat-induced increase of antioxidant activity in the peel showed a strong significant correlation only with the contents of total phenolics (r2 = 0.9493) and total hydrolysable tannins (r2 = 0.9288), suggesting that the main antioxidant contributors differ from the flesh.
Oxidative Damage in Korean Medicine
Authors: Park Gunhyuk
Published: March 2022

Korean medicine originated in ancient and prehistoric times, as evidenced by the discovery of stone and bone needles in the North Hamgyeong Province, dating back to 3000 BC [...]
Membrane-Free Stem Cells and Pyridoxal 5′-Phosphate Synergistically Enhance Cognitive Function in Alzheimer’s Disease Mouse Model
Authors: Choi Ji Myung , Park Hye Sook , He Mei Tong , Kim Young Sil , Kim Hyun Young , Lee Ah Young , Cho Eun Ju
Published: March 2022

Accumulation of amyloid beta (Aβ) is a major pathological hallmark of Alzheimer’s disease (AD). In this study, we evaluated the protective effect of membrane-free stem cell extract (MFSCE), which is a component of adipose-tissue-derived stem cells, on cognitive impairment in Aβ25–35-injected AD mice. The ICR mice were i.c.v. injected with Aβ25–35 and then treated with MFSCE for 14 days (i.p.). The Aβ25–35-injected mice showed deficits in spatial and object perception abilities, whereas treatment with MFSCE inhibited Aβ25–35-induced learning and memory impairment in the T-maze, novel object recognition, and Morris water maze tests. Moreover, Aβ25–35-induced lipid peroxidation and nitric oxide overproduction were attenuated by treatment with MFSCE. These antioxidant effects of MFSCE were related to the inhibition of the apoptotic signaling pathway. In particular, the combination treatment of MFSCE and pyridoxal 5′-phosphate (PLP) showed greater suppression of Bax and cleaved caspase-3 protein expression compared to the MFSCE- or PLP-only treatment. Furthermore, the MFSCE and PLP combination significantly downregulated the amyloidogenic-pathway-related protein expressions, such as amyloid precursor protein, presenilin 1, and presenilin 2. Therefore, the MFSCE and PLP combination may synergistically prevent Aβ25–35-induced neuronal apoptosis and amyloidogenesis, which contributes to cognitive improvement and has potential therapeutic implications for AD patients.
Estimation of Hydrogeological Parameters by Using Pumping, Laboratory Data, Surface Resistivity and Thiessen Technique in Lower Bari Doab (Indus Basin), Pakistan
Authors: Akhter Gulraiz , Ge Yonggang , Hasan Muhammad , Shang Yanjun
Published: March 2022

Determination of hydrological properties of the aquifer is of fundamental importance in hydrogeological and geotechnical studies. An attempt has been made to refine the hydraulic conductivity values computed from the pumping test by utilizing the hydraulic values computed in the laboratory. This study uses hydraulic conductivity computed in the laboratory of rock samples, pumping test data in conjunction with the empirical equations, and vertical electric sounding (VES) to determine the hydraulic properties of Lower Bari Doab (LBD) in the Indus Basin of Pakistan. The utilized dataset comprises pumping test results (Kpump) from 17 water wells, hydraulic conductivity values (Klab) of different grain size subsurface lithologies, and 50 VES stations. To this end, the investigated area is divided into 17 polygons by using the Thiessen technique, and equal distribution/weight of conductivities values is assigned to 17 polygons (one polygon around each water well where pumping test is conducted). The true resistivity ranging from 20–90 ohm-m along with an average thickness of the aquifer is computed using the VES data for each polygon. A novel approach has been developed to estimate the hydraulic conductivity of the aquifer by combining laboratory data and pumping test which is used to compute the other hydraulic properties. The calculated hydraulic conductivity, transmissivity, and tortuosity values of the aquifer range from 4.4 to 85.6 m/day, 674 to 8986 m2/day, and 13 to 20, respectively. The porosity ranges from 32 to 45% and the formation factor values fall in the range 4 to 12. Higher hydraulic conductivities were encountered in the southern portion of the area near the junction of the rivers, and it increases with an increase in porosity. The aquifer having T > 5700 m2/day and K > 40 m/day, yields a large quantity of water whereas the portion of an aquifer with T < 1100 m2/day and K < 13 m/day are combatively low yield aquifer. The results of the resistivity method show that the subsurface geological material, as depicted from true resistivity, is composed of layers of sand, clay, and silt mixed with gravel/sand. This study improves the understanding of the aquifer and will help in the development and management of groundwater resources in the area including the prediction of future behavior of the aquifer.
Fluid Flow Development in a Pipe as a Demonstration of a Sequential Change in Its Rheological Properties
Authors: Nikushchenko Dmitry , Pavlovsky Valery , Nikushchenko Elena
Published: March 2022

The sequence of the process of changing the velocity profiles and the laws of resistance during the flow of a fluid in a pipe is considered. With the increasing of the Reynolds number, we obtain the transition of the flow regime from laminar to turbulent. In the presence of small additives of polymers, when the Toms effect is observed in the fluid flow, the turbulent regime changes with a further increase in the Reynolds number to another regime, the rheology of which leads to laminar velocity profiles and corresponding resistance laws. Then, with an increase in the Reynolds number for polymer solutions, the limiting Virk flow regime with its own rheology is reached. All the mentioned flow regimes and all types of rheology can be described using one rheological relation, which is a power-law generalization of Newton’s formula, by changing the values of the power value in this ratio upon reaching the corresponding critical Reynolds numbers. This generalization can be extended to the spatial case of flow and the rheological relation can be represented in tensor form with a further system of differential equations for a fluid flow with an arbitrary rheology. After that, boundary value problems in fluid mechanics can be solved for any fluid flow regime.
A Method for Maximum Coverage of the Territory by Sensors with Minimization of Cost and Assessment of Survivability
Authors: Petrivskyi Volodymyr , Bychkov Oleksii , Shevchenko Viktor , Martsenyuk Vasyl , Bernas Marcin
Published: March 2022

In the modern technological world, there are several key factors in the construction of sensor networks. These include maximizing the coverage and minimizing the cost of the network. Like any information system, the sensor network must also meet the conditions of survivability. This is why the development of a method for assessing the survivability of the sensor network is also a key factor. The purpose of this study is to develop a method to establish the maximum coverage of the territory of the sensor network at minimum cost with the ability to assess the survivability of the network. Coverage maximization while minimizing the network’s cost is achieved by finding the optimal pair of values of the coverage radius and the level of the intersection of coverage areas. These values are found by solving a nonlinear multicriteria optimization problem with the use of the genetic algorithm. The designed method for estimating the survivability of sensor networks takes into account not only the importance of network components but also the bandwidth of the network elements. The result of using the proposed methods is a set of Pareto optimal pairs of values of the radii of coverage and the value of the intersection of the coverage areas. In the case of network survivability assessment, the result, in addition to the percentage assessment, is a set of vulnerable sensors and network communication channels. The proposed network survivability estimation method improved the estimation accuracy by 18% compared to methods used in previous works.
Viability Study of the Application of Bi-Block Concrete Sleepers as a Solution for Technical Landfills
Authors: Másmela Camilo , Teixeira Elisabete , Tinoco Joaquim , Matos José Campos e , Mateus Ricardo
Published: March 2022

Transition zones, specifically embankment structures on railway tracks, are recurrently damaged by high-speed rail traffic, thus producing abrupt variations in the track vertical stiffness. The main objective of this work is to study the implementation of Construction and Demolition (C&D) wastes, specifically Bi-Block (BB) concrete sleepers, to minimize the issues related to the differences in stiffness along the area of the technical landfills, using unconventional environmental solutions. The use of BB wastes can reduce the environmental impacts caused by the construction sector. The studied solutions produce similar stiffness levels to traditional solutions. The Multicriteria Decision Support Methodology for the Relative Sustainability Assessment of Building Technologies (MARS-SC) allows concluding that the studied solutions are more sustainable than the traditional ones.
A Deep Reinforcement Learning-Based Scheme for Solving Multiple Knapsack Problems
Authors: Sur Giwon , Ryu Shun Yuel , Kim JongWon , Lim Hyuk
Published: March 2022

A knapsack problem is to select a set of items that maximizes the total profit of selected items while keeping the total weight of the selected items no less than the capacity of the knapsack. As a generalized form with multiple knapsacks, the multi-knapsack problem (MKP) is to select a disjointed set of items for each knapsack. To solve MKP, we propose a deep reinforcement learning (DRL) based approach, which takes as input the available capacities of knapsacks, total profits and weights of selected items, and normalized profits and weights of unselected items and determines the next item to be mapped to the knapsack with the largest available capacity. To expedite the learning process, we adopt the Asynchronous Advantage Actor-Critic (A3C) for the policy model. The experimental results indicate that the proposed method outperforms the random and greedy methods and achieves comparable performance to an optimal policy in terms of the profit ratio of the selected items to the total profit sum, particularly when the profits and weights of items have a non-linear relationship such as quadratic forms.
Discrete HMM for Visualizing Domiciliary Human Activity Perception and Comprehension
Authors: Kuan Ta-Wen , Tseng Shih-Pang , Chen Che-Wen , Wang Jhing-Fa , Sun Chieh-An
Published: March 2022

Advances in artificial intelligence-based autonomous applications have led to the advent of domestic robots for smart elderly care; the preliminary critical step for such robots involves increasing the comprehension of robotic visualizing of human activity recognition. In this paper, discrete hidden Markov models (D-HMMs) are used to investigate human activity recognition. Eleven daily home activities are recorded using a video camera with an RGB-D sensor to collect a dataset composed of 25 skeleton joints in a frame, wherein only 10 skeleton joints are utilized to efficiently perform human activity recognition. Features of the chosen ten skeleton joints are sequentially extracted in terms of pose sequences for a specific human activity, and then, processed through coordination transformation and vectorization into a codebook prior to the D-HMM for estimating the maximal posterior probability to predict the target. In the experiments, the confusion matrix is evaluated based on eleven human activities; furthermore, the extension criterion of the confusion matrix is also examined to verify the robustness of the proposed work. The novelty indicated D-HMM theory is not only promising in terms of speech signal processing but also is applicable to visual signal processing and applications.
Modern and Dedicated Methods for Producing Molecularly Imprinted Polymer Layers in Sensing Applications
Authors: Gavrilă Ana-Mihaela , Stoica Elena-Bianca , Iordache Tanţa-Verona , Sârbu Andrei
Published: March 2022

Molecular imprinting (MI) is the most available and known method to produce artificial recognition sites, similar to antibodies, inside or at the surface of a polymeric material. For this reason, scholars all over the world have found MI appealing, thus developing, in this past period, various types of molecularly imprinted polymers (MIPs) that can be applied to a wide range of applications, including catalysis, separation sciences and monitoring/diagnostic devices for chemicals, biochemicals and pharmaceuticals. For instance, the advantages brought by the use of MIPs in the sensing and analytics field refer to higher selectivity, sensitivity and low detection limits, but also to higher chemical and thermal stability as well as reusability. In light of recent literature findings, this review presents both modern and dedicated methods applied to produce MIP layers that can be integrated with existent detection systems. In this respect, the following MI methods to produce sensing layers are presented and discussed: surface polymerization, electropolymerization, sol–gel derived techniques, phase inversionand deposition of electroactive pastes/inks that include MIP particles.